Polymeric Microcapsules With Ligth Responsive Properties for Encapsulation and Release

Advances in Colloid and Interface Science 158 (2010) 2–14

Contents lists available at ScienceDirect

Advances in Colloid and Interface Science

j ourna l homepage: www.e lsev ie r.com/ locate /c is

Polymeric microcapsules with light responsive properties for encapsulationand release

Matthieu F. Bédard a,b, Bruno G. De Geest c, Andre G. Skirtach b, Helmuth Möhwald b, Gleb B. Sukhorukov a,⁎a Queen Mary, University of London, School of Engineering and Materials Science, London E1 4NS, UKb Max Planck Institute of Colloids and Interfaces, Department of Interfaces, Potsdam 14424, Germanyc Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, GhentUniversity, Ghent, Belgium

⁎ Corresponding author. Tel.: +44 20 7882 5508; faxE-mail address: [email protected] (G.B. Suk

0001-8686/$ – see front matter © 2009 Published by Edoi:10.1016/j.cis.2009.07.007

a b s t r a c t
a r t i c l e i n f o
Available online 3 August 2009

Keywords:MicrocapsulesPolyelectrolytesLayer-by-layerDrug deliveryMetal nanoparticlesEncapsulationUVIRPorphyrinAzobenzene

This review is dedicated to recent developments on the topic of light sensitive polymer-based microcapsules.Themicrocapsules discussed are constructed using the layer-by-layer self-assemblymethod, which consists inabsorbing oppositely charged polyelectrolytes onto charged sacrificial particles. Microcapsules display a broadspectrum of qualities over other existing microdelivery systems such as high stability, longevity, versatileconstruction and a variety of methods to encapsulate and release substances. Release and encapsulation ofmaterials by light is a particularly interesting topic. Microcapsules can be made sensitive to light byincorporation of light sensitive polymers, functional dyes andmetal nanoparticles. Optically active substancescan be inserted into the shell during their assembly as a polymer complex or following the shell preparation.Ultraviolet-addressablemicrocapsules were shown to allow for remote encapsulation and release ofmaterials.Visible- and infrared- addressable microcapsules offer a large array of release strategies for capsules, fromdestructive to highly sensitive reversible approaches. Besides the Introduction and ,Conclusions, this reviewcontains in four sections reviewing the effects of light 1) on polymer-based microcapsules, 2) microcapsulescontaining metal nanoparticles and 3) functional dyes, as well as a fourth section that revisits the implicationsof light addressable polymeric microcapsules as a microdelivery system for biological applications.

© 2009 Published by Elsevier B.V.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.1. Preparation of polyelectrolyte microcapsules and proximal factors for encapsulation and release . . . . . . . . . . . . . . . . . . . . 31.2. Magnetism, ultrasound and microwaves as external triggers for release . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41.3. Light addressable strategies to affect microcapsule permeability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

2. Effect of ultraviolet light on polymer-based microcontainers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42.1. Destruction of polymer-based microcapsules by UV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42.2. Microcapsules containing azobenzene moieties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

3. Metal and metal oxide nanoparticles in microcontainers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63.1. Titanium oxide nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63.2. Silver nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73.3. Gold nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73.4. Gold nanoparticles aggregates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83.5. Gold nanorods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

4. Functional dyes for remote capsule activation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104.1. Fluorescent dyes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104.2. Porphyrinoid dyes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

5. Light addressable microcapsules for cell studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115.1. Cell studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115.2. Intracellular fates of optically released materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

: +44 20 7882 3390.horukov).

lsevier B.V.

mailto:[email protected]

http://dx.doi.org/10.1016/j.cis.2009.07.007

http://www.sciencedirect.com/science/journal/00018686

3M.F. Bédard et al. / Advances in Colloid and Interface Science 158 (2010) 2–14

1. Introduction

Selective permeability is an essential attribute of membranes. Theability of certain ions and molecules to pass across membranes ofliving cells is the result of biological compartmentalization thatseparates certain cellular components into sub-environments appro-priate to carry on their activities. Microencapsulation technologiesinspire themselves from natural occurrences to create artificialmicron- and nano-sized containers with the ability to encapsulateor release substances with the help of triggers. Over the last 50 years,there were reports on various hollow shells with the capability toencapsulate and release materials. However, most of these present afragile construction and come with many limitations in terms of thetemplate materials that could be used and the shell constituents.

In the 1990s Decher and the group led by Möhwald (MPI-KG,Germany) developed and perfected the electrostatic self-assembly(ESA)method [1] (first proposed by Iler in 1966 [2]) bywhich thin filmscan be repetitively deposited onto a surface to produce multilayeredfilms. Unlike multilayer films obtained by the well establishedLangmuir–Blodgett deposition technique for instance, ESA was com-pletely indifferent to the type of substrate used so long as it is charged.The driving force for ESA resides in creating a surface charge excess, orovercompensation, at the interface of a material of interest. Thistechnique is now commonly referred to as layer-by-layer (LbL)assembly. Originally designed on planar surfaces, LbL films were soonused to coat colloidal particles which are later dissolved to producehollow polymeric shells (Fig. 1.1) [3,4]. LbL polymeric microcapsulespossess significant advantages over other types of microshells (e.g.micelles, liposomes, and inorganic hollow shells) notably in theirmechanical behavior and the possibility to control shell composition,thickness, stiffness, roughness, density, hydration, diameter andpermeability to various degrees [5–7]. Emulsion-based microcapsulesand encapsulation of substances within them was demonstrated asearly as the 1960s,with the publication of amethod to stabilize dropletsof organic solvents in aqueous media using polyelectrolytes [8].

This review is meant to give to the reader an overview of the recentdevelopment on the optical approaches for the release and encapsula-tion of substances using polymer-based microcapsules. Microcapsulesconstructed of polyelectrolytes only, or impregnatedwith dyes ormetalnanoparticles were shown to exhibit different types of behavior when

Fig. 1.1. Schematic of the LbL assembly of polymeric microcapsules. The procedurebegins by coating a charged colloid with a polyelectrolyte of opposite charge (1). Anoppositely charged molecule (2) or polyelectrolyte (3) can then be used to coat the firstlayer. These steps may be repeated taking care to alternate the charge of the coatingmaterial at each addition. The subsequent decomposition of the template (4) yields ahollow polymeric shell.

irradiated with light from the near-UV to near-IR region of theelectromagnetic spectrum. For microcapsules built of polyelectrolytesonly, the effects of UV have been investigated. In Section 2, it will beshown that UV irradiation has a strong effect on the chemicalcomposition of capsules, yet can also be used to encapsulate substances.Small molecules such as dyes are typically used for visualizationpurposes. In Section 3, we will discuss howmetal nanoparticles such asTiO2, silver and gold can be used both, to destructively and non-destructively change the permeability and mechanical attributes ofmicrocapsules when exposed to light. In Section 4, the effects of visibleand IR irradiation on the stability and morphology of microcapsulescontaining fluorescent and functional dyes will be presented. Finally,Section 5 gives the reader a brief summary of the recent biologicalstudies using these optically addressable microshells. The review is anattempt to summarize theworkdone in the pastfive years aswell as thecurrent developments on the topic of light addressable polymericmicrocontainers. Recently emerging challenges and newly foundsolutions in using these capsules for in vivo studies suggest that thetopic of optically addressable microshells is on the rise.

1.1. Preparation of polyelectrolyte microcapsules and proximal factorsfor encapsulation and release

The preparation procedures of LbL polymeric microcapsules havebeen thoroughly described in the literature and are summarized inFig. 1.1 [5]. Briefly, capsules are constructed in solution using one oftwo self- assembly procedures: 1) sequential additions of polymersolution, followed by centrifugation to separate the coated colloidsfrom the supernatant, and 2) using amicro-filtration setup that allowsthe removal of supernatant without the extra steps of centrifugation.Microcapsules can be constructed on solid particles, liquid dropletsand more recently microbubbles. The latter two templates are morefragile and challenging to manipulate and are occasionally used tostabilize multiphase systems. Solid sacrificial templates can be oforganic nature (latexes and gel beads) or inorganic micro- andnanometer sized particles (silica and CaCO3) [9–11].

The shell constituents usually require the use of at least onepolyelectrolyte and can be anything with sufficient charge density,from synthetic polyelectrolytes to sugars and DNA. The creation oflayers composed of small or low charge density molecules byelectrostatics can be difficult since all the charges on low molecularweight materials can easily find a countercharge, neutralizing thesurface charge as opposed to reversing it. Amongst recently publishednovelties in the production of single component microcapsules,emphasis can be put on the use of chemical cross-linking [12–16]and click chemistry [17–20] which enabled to fix small molecules orsame chargematerials intomultilayer complexes, or to strengthen theLbL film. Diblock copolymers were also used to produce singlecomponent microcontainers [21]. Recently, Wang et al. constructedthick-walled microcapsules using a mesoporous substrate [22,23]treated with a single layer of polyelectrolyte and chemically cross-linking the polymers before dissolving the template [14].

Polyelectrolyte microcapsules have a number of interestingproperties and carry a great potential for diverse applications. Forone, capsules are essentially semi-permeable membranes withselective permeability to certain molecules. Controlling the perme-ability of the thin shell of microcontainers is perhaps the mostchallenging and interesting topic in the area of micro-encapsulation.Encapsulation of a substance that initially permeates the LbL micro-shells can be accomplished by increasing the wall density, eitherchemically (i.e. forming cross-links in the shell) or by physical means.The latter involves changing the permeability of microcapsules usingone of various strategies including light [24,25], solvent exchange[26,27], high temperature [28–31] and pH [32–35]. Another way toencapsulate a substance that initially does not permeate the shell is byco-precipitationwith CaCO3 and use of the loaded CaCO3 as a sacrificial

4 M.F. Bédard et al. / Advances in Colloid and Interface Science 158 (2010) 2–14

template for the capsules [36–39]. Emulsion–emulsion synthesizedmicrogels constitute alternative templates for microcapsule construc-tion [40–42]. The most important consequence of being able todecrease the permeability of microcapsules is, therefore, the possibil-ity to encapsulate substances in the cavity of the microcontainer.

Triggers that can be used to release encapsulated substances fromthe microcapsule cavity [43] can be grouped in two categories: 1)proximal triggers that require a physical interaction with the capsulesolution or the capsules themselves and 2) external triggers, whichrequire no interaction or alteration of the capsule or capsule solutionproperties. Proximal triggers that were found to affect LbL capsulesinclude the application of force on the capsule to damage it. Physicalinteractionwas used to study themechanical behavior ofmicrocapsulesand determine the parameters that improve their resistance todeformation [44–49]. Other proximal triggers to induce release ofmicrocapsules require softening the electrostatic interactions changingsolutionparameters such aspHand ionic strength [30,32,33,50,51], or inthe case of capsules built from biological polyions (e.g. DNA, polypep-tides, and polysaccharides), the addition (or presence) of appropriateenzymes [36,37]. However, for many applications such as biomedical orsurface coating technologies, it is desirable to address the microcontai-ner using external means that require no direct interaction with thecapsule medium.

1.2. Magnetism, ultrasound andmicrowaves as external triggers for release

External triggers with the ability to affect microstructures come inthe form of magnetic force as well as in three flavors of electromag-netic waves; ultrasonic, microwaves and light. The development ofmicrocontainers that are highly sensitive to any of these triggers hasimportant implications, especially in the fields of health and surfacesciences, where sometimes microdelivery systems cannot beaddressed with proximal triggers. The magnetic force is usedprimarily to localize and visualize materials that contain magneticor paramagnetic constituents [37,52]. Lu et al. were able to use analternating magnetic field to change the permeability of microcap-sules impregnated with Co–Au core–shell nanoparticles [53]. Themagnetic field in this case, induced the nanoparticles to rotatedamaging the shell, irreversibly increasing the wall permeability. Aclear example of release of encapsulated material using magnetism asa remote trigger was demonstrated very recently by Hu et al. [54].Magnetic microcapsules with an anti-cancer drug could allow themedical practitioner to position and localize the microcontainersaround a target area of sick tissue, minimizing the dose necessary andthe corresponding side effects of the treatment [55].

Ultrasound radiation with frequencies in the order of kilo andmega Hertz (20 kHz–10MHz) are extensively used for the synthesis ofnanomaterials [56–58] as well as for imaging and diagnostic purposesin medicine [59–62]. Ultrasound can lead to the cavitation andcollapse of microbubbles from dissolved gases, a highly energeticprocess with the capability of breaking molecular bonds [63]. Takingadvantage of this effect, ultrasound was recently introduced as analternative approach to release encapsulated materials from poly-meric microcapsules [64–67]. Microwaves on the other hand, possessshorter waves than ultrasound spanning electromagnetic frequenciesbetween 0.3 GHz and 300 GHz. Microwaves have more subtleinteractions with matter than ultrasound and are not energeticenough to ionize matter. It was recently shown that microwaves canbe used to control the aggregation of proteins [68,69]. Gorin et al.demonstrated that low intensity microwaves (2–8 GHz) can lead tothe destruction of LbL microcontainers [70]. The destructive effect ofmicrowave exposure was especially strong in shells that containedsilver nanoparticles. This nanoparticle–microwave interaction couldbe another promising approach to remotely affect the properties ofcapsules. Light radiation with wavelength in the approximate range200–1200 nm is the most studied type of remote trigger used with

polymeric capsules. The remaining of this text will be dedicated to thevarious aspects of optically addressable polymeric microcapsules. Oneof the prominent applications of microcapsules is intracellulardelivery and release [71]. In this regard, the optical (or morespecifically near-IR~800 nm) spectral range is one of the mostbiologically friendly regions of the electromagnetic spectrum.

1.3. Light addressable strategies to affect microcapsule permeability

One of the priorities of recent research on polymeric microcontai-ners has been to control the shells' permeability using mild externaltriggers such as light. The first studies to remotely release encapsu-lated materials from microcapsules involved the use of pulsed(modulated) laser sources or microcontainers doped with very largeamounts of metal nanoparticles, both resulting in the destruction ofthe microcontainer [72,73]. Concerns with regards to the explosivedestruction of microcontainers in various applications and thepotential toxicity [74] of metal nanoparticles in cells led to focus theresearch on significantly reducing the radiation energy requirementsfor capsule activation and minimizing the concentration of lightsensitizing agents in microshells.

2. Effect of ultraviolet light on polymer-based microcontainers

The main constituents of LbL microcapsules are polymers consistingprimarily of atoms of oxygen, carbon, nitrogen and hydrogen heldtogether by covalent bondswith energies of the order of 100kcal·mol−1.Far- UV irradiation (λb200 nm) is energetic enough to ionize covalentbonds of such polymers (and most molecules around them) andtherefore polymeric microcapsules are assumed to absorb irradiationat far-UVwavelengths. At sufficient intensity, the saturated bonds of thepolymers are cleaved by laser ablation, the thermodynamic process bywhich bonds within molecules are broken upon absorption of photons[75,76].However, theunderlyingmechanismsofpolymer ablationunderfar-UV irradiation are complex and not suited for this review [77].Because of its highly unspecific, destructive nature towards organicmaterials, far-UV is not a useful source of irradiation to control theencapsulation and release of relatively fragile structures such aspolyelectrolyte microcapsules. At longer wavelengths (N200 nm),specific absorption may occur in polyelectrolytes but in this casecorrelateswith othermaterials or chromophores present in the capsules,such as nanoparticles or unsaturated side chains attached to thepolymers. Many polyelectrolytes discussed in the literature, whichwere used in the construction of LbL capsules absorb somewhere in thenear-UV region (~200–400 nm). This section summarizes thoseinvestigations on the effects of near-UV irradiation of microcapsulesbuilt from polyelectrolytes only.

2.1. Destruction of polymer-based microcapsules by UV

Experiments using a pulsed laser (Nd:YAG, B.M. Industries, YAG502 DPS 7910DP) operating at 355 nm and fluence up to 1 J/cm2 toirradiate microcapsules built from polymers such as poly(allylaminehydrochloride) (PAH), (PDADMAC), poly(vinylsulfonate) (PVS) andaromatic containing poly(styrene sulfonate) (PSS) were conducted(unpublished results). None of these polymers absorb significantly at355 nm. Irradiation of microcapsule solutions was found to leave thecapsules undamagedwhen using relatively low laser fluence (b40mJ/cm2) after an exposure time of up to 1 h (35 ps per pulse, repetitionrate of 10 Hz). Between energy densities of 40 and 100 mJ/cm2

capsules remained unaffected or became deformed after a few pulses.This is illustrated in Fig. 2.1 before (A) and after (B) exposure to theUV laser beam for (PAH/PSS)4 microcapsules at a fluence of 70 mJ/cm2. At fluence greater than 100 mJ/cm2, the microcontainers becameseverely damaged. This is shown in Fig. 2.1 D where capsules (C) wereirradiated with 10 pulses at 200 mJ/cm2 resulting in some shells

Fig. 2.1. Ablation effects on (PAH/PSS)4 microcapsules in water after exposure to pulsedUV irradiation at 355 nm. Top: three capsules before (A) and after exposure to 20 laserpulses at a fluence of 70 mJ/cm2 tend to deform or break. Bottom: five capsules before(C) and after (D) exposure to 10 laser pulses at a fluence of 200 mJ/cm2 are oftencompletely destroyed.


appear ing as if cut to pieces. Because the investigated capsules lackedstrong absorption, this effect can be attributed to (1) pressure of light[78–80] acting on relatively weak capsules [44,45], (2) weak absorp-tion and strong field and (3) plasma generation (which depends onfactors such as; molar absorptivity of the irradiated material, pene-tration depth of the laser beam and irradiation wavelength used [75]).While capsules damaged by this approach could also be effectivelyopened to release encapsulated substances, UV ablation is a veryenergetic process which could equally damage the encapsulated sub-stance. To avoid these undesirable effects, much milder approaches,such as longerwavelengths, continuouswave (CW) lasers or lamps arepreferable for microcapsule applications involving remotely address-able encapsulation and release.

The effects of CW near-UV irradiation on microcapsules were alsoinvestigated [25,81]. Katagiri et al. demonstrated that the irradiatedLbL capsules containing near-UV absorbing chromophores (i.e. PSS/PDADMAC, DNA/PAH, PSS/PAH) are degraded to various oligomers,ions, radicals and oxides [81]. From their observations it wasconcluded that the decomposition products originated from thedestruction of capsule materials that absorb significantly in the near-UV such as the aromatic styrene groups of the polymer PSS, whichpossesses an absorption maximum at ~225 nm. The capsulesremained seemingly unaffected by UV when constructed from onlynon-aromatic polymers [81]. A second notable effect of capsuleirradiation with CW near-UV was that the shells had a tendency toshrink during illumination [81], which is relevant because shrinkagecould mean wall densification and the possibility to encapsulatedmaterials. In such capsules, however, the diameter decreased similarlyfor shells with an even and uneven number of layers putting aside UV-induced heating as a causative parameter for shrinkage. Changes incapsule diameter due to temperature belong to an important entropyrelated effect of polyelectrolyte microcapsules that is a direct con-sequence of the charge balance across the shell [82].

Heat-shrinkage of microcapsules as a function of LbL structure wasthoroughly investigated by Köhler et al. who noted that shellsconstructed with an even number of layers tended to shrink uponheating, while built from an uneven number of layers the shells becomelarger [82]. The opposing behaviors upon heating the capsules are

attributed to a balance between two forces; (1) hydrophobic surfaceforces and (2) electrostatic repulsive forces due to like charges [83,84].For example, when the net charge across the capsule wall is close toneutrality the hydrophobic main chains of the polymers within the shellforce this one tominimize its surface area in contactwithwater, resultingin the capsule shrinking. It should be noted that this effect can bedifferent, see completely reversed depending on the solution properties(e.g. pH and buffer) [85]. Since no thermal related effects were found forshrinking capsules irradiated with UV, it can be assumed that UV effectsare predominantly of chemical origin rather than physico-chemical.

A far more versatile approach to sensitize microshells to UVirradiation, however, involves impregnating polymer capsule con-structs with metal oxide photocatalytic nanoparticles (e.g. TiO2) toform polymer/nanoparticle composite films. This will be discussed inmore detail in Section 3.1.

2.2. Microcapsules containing azobenzene moieties

An interesting group of molecules that responds to both near-UVand visible light are azobenzenes. An azobenzene molecule containstwo phenyl groups joined by a azo (N=N) bond [86]. Azobenzenegroups respond to UV absorption by undergoing reversible internalrearrangements termed cis-trans (Z–E) isomerizations (Fig. 2.2).Thermal isomerization typically occurs from the least stable cis tothe most stable trans moiety (Z→E), while optical isomerization canoccur either way. At themolecular level, these cis-trans isomerizationscome with significant changes in terms of molecular geometry andpolarity, but they are rather weak when incorporated in macro-systems. The largest of absorbance region of azobenzene molecules issituated in the near-UV (Fig. 2.2, Π→Π⁎) but can extend to thevisible range depending on the phenyl substitution, solvent and otherfactors [87]. A second less intense absorption region (Fig. 2.2, n→Π⁎)is typically located at longer wavelengths. Fig. 2.2 illustrates that theintensity of the two peaks varies oppositely depending on the degreeof cis-trans isomerization. Cis-trans isomerization is often reversibleand it was shown very recently that lipid vesicles containing azomoieties could be made to bud into multiple vesicles upon UV lightexposure and fuse with one another when exposed to green light [88].Diazoresins (DZR) were shown to form covalent bonds with poly(acrylic acid) or PSS in LbL films upon UV irradiation [13,89–92].Similarly, composite shells of diazoresin (DZR) and PSS could bepolymerized by exposure to ultraviolet light [93,94]. The resultingcross-linked DZR/PSS microcapsules displayed superior mechanicalstability over capsules that were not exposed to light [94].Photoisomerization in LbL films on planar support and microcapsuleswas shown using main chain polyazo molecules as a mean to destroypolymer aggregates by optically forcing cycles of trans-cis-transisomerization within the films [95].

The incorporation of the azobenzenemolecule Brilliant Yellow (BY)in LbL films of the type BY/PAH showed slow isomerization kinetics incomparison to pure azo films [96]. Additionally, isomerization in suchfilms was irreversible whereas photodegradation was detected at lowlevels. The potential use of azobenzene molecules to control thepermeability ofmicrocapsuleswas briefly investigated [97]. Reversibleisomerization of azobenzene groups in LbLfilmswas shown to occur invarious films [98–100] including some containing the polyanion poly{1-4[4 -(3-carboxy-4-hydroxyphenyl-azo)benzene-sulfonamido]-1,2-ethanediyl} (PAZO) [101–103]. PAZO is a polyelectrolyte withcarbonated azobenzene side chains and aΠ→Π⁎absorption centeredat 366 nm. This polyelectrolyte was used in the design of capsules thatshrink upon UV exposure in the study of the optical properties of goldnanoparticles attached to the shell [104].

LbL films constructed with PAZO were used to develop the firstlight induced encapsulation strategy for polymer microshells [25].Azobenzene-substituted PAH with substitution ratio from 1 to 10%,were used to assemble LbL microcapsules. Cis-trans isomerization was

Fig. 2.2. Cis-trans isomerization of azobenzene molecules upon irradiation. Top and middle panels: exposure to light in the 300–400 nm window (pink) typically leads to an E→Zconformational change whereas heat or exposure to light at wavelengths above 400 nm (blue) favors the Z→E change. A change in conformation in the E→Z direction isaccompanied by a decrease in the main Π→Π⁎absorption peak and a small increase in the n→Π⁎ region. The spectroscopic changes are reversible. Bottom panel: confocalmicroscope image of (PAH/PAZO)n/PVS capsules, showing that the shell is permeable to fluorescent dextran, before UV irradiation (A) and washing the supernatant left emptycapsules (B). Encapsulation of the fluorescent dextran (C) occurred after exposure of the capsules to UV light in the presence of fluorescent dextran. Figure reprinted from [25].Copyright Wiley-VCH Verlag GmbH & Co. KGaA.


detected in those polymers but failed to occur when these werepresent in a LbL system of the type (Azo-PAH/PSS)n or (Azo-PAH/PVS)n (unpublished results). Alternatively, microcapsules built fromthe polyelectrolytes PAH, PAZO and PVS to obtain the construction(PAH/PAZO)n/PVS were reported to shrink and allow the encapsu-lation of macromolecules after irradiation under near-UV light (300–400 nm); however, the permeability change was found to beirreversible [25]. PAH and PVS possess no significant absorption forthis irradiation. Heating the capsules up to 90 °C for prolonged timedid not lead to shrinking and local rearrangements due to annealingeffects were excluded.

3. Metal and metal oxide nanoparticles in microcontainers

Metal and metal oxide nanoparticles lend themselves to a varietyof applications from the formation of inorganic thin films with welldefined pore size [105] and the catalytic synthesis of othernanoparticles [106,107], to the formation of polymer/nanoparticlescomposite films [108]. Nanoparticles of silver and gold absorb light inthe visible spectrum and release this energy as heat in theirsurroundings [109–112]. This is due to surface plasmon resonanceabsorption of the nanoparticles, whose absorption cross-section is

drastically more intense (N106) than for a typical dye. In the case ofsilver and gold, these oscillations termed plasmons have frequenciesof approximately 425 nm and 525 nm, respectively. The heatproduced by such nanoparticles can be harvested to releaseencapsulated substances from microcapsules destructively (1) ornon-destructively (2) as illustrated in Fig. 3.1. A review onnanoparticle-modified polymeric capsules with much emphasis onthe biological applications of such shells was recently published [55].

3.1. Titanium oxide nanoparticles

Titanium dioxide particles and related composites are well knownfor their catalytic activity and oxidative potential [105,113]. They havelow production costs and a strong absorbance in the UV, making suchnanoparticles a smart choice of compound to sensitize thin films to UVlight [114,115]. Several reports have been already published on theincorporation of TiO2 nanoparticles into microcapsules, via in-situsynthesis of the nanoparticles within films [116–119], doping[106,120], as a component layer in LbL films [121] and as anencapsulated substance [122]. Katagiri et al. showed that organic–inorganic microcontainers impregnated with TiO2 rupture uponexposure to UV light at relatively low intensity (5–20 mW cm−2)

Fig. 3.2. Laser opening of a shell-in-shell type microcontainer. The inner container isfunctionalized with gold nanoparticles and can be opened by light while the outercompartment remains unaffected. Figure reprinted from [37]. Copyright Wiley-VCHVerlag GmbH & Co. KGaA.

Fig. 3.1. Schematic of the two possible release scenarios of encapsulated material by thelaser nanoparticle interaction. (1) Upon illumination, the nanoparticles produce a largeamount of heat that breaks the capsule wall open. (2) During illumination, thenanoparticles produce a small quantity of heat sufficient to exceed the glass transitionof the polymer complex of the capsule, decreasing the shell's permeability untilillumination is stopped. The increased permeability allows for encapsulated material tobe released from the capsules without the shell being damaged.


[118]. The organic part of such hybrid capsules contributes toconsiderably reduce the permeability of the shell to small hydrophilicmaterials. Such capsules have a great potential as a container for self-healing coatings [123,124] where light activated release could betriggered by any irradiation source. This system would also beparticularly interesting as a drug delivery candidate if; (1) inorganictemplates (e.g. CaCO3 and SiO2) instead of melamine formaldehyde(MF) particles, which are known to affect the microcapsulesmechanics and leave toxic melamine oligomers in the shell structureafter core decomposition [125,126], (2) visible or near-IR addressableparticles were incorporated in the structure [127,128]. An overview ofvarious templates for microcapsules and various encapsulation andrelease mechanisms was recently published [129].

3.2. Silver nanoparticles

The use of noble metal nanoparticles to optically induce changes inthe shell of microcapsules was first demonstrated by Skirtach et al.who doped silver nanoparticles into PAH/PSS microshells and studiedtheir response to light irradiation [73]. Absorption of light in thesurface plasmon spectral region of the nanoparticles results in heatproduction that can affect the capsule wall (Fig. 3.1). The mainabsorption region of silver nanoparticles spans the 380–430 nmwavelengths and the position of its absorption maximum dependslargely on the size and shape of the particles [130,131]. The use ofwavelengths in the main absorption region of silver nanoparticles isnot ideal for therapeutic treatments such as drug or gene deliverysince many biological molecules absorb light outside the so-called“biologically friendly window”, i.e. 700–1000 nm. The residualabsorption of silver nanoparticles with a diameter of 20 nm in thenear-IR was shown to be sufficient to produce heat and breakmicrocapsules [73] but insufficient for microcapsules containing 4 nmsilver nanoparticles [132]. The irradiation time necessary to breakmicrocapsules also depends on the size of the nanoparticles. Using a532 nm CW laser, Radzuik et al. showed that capsules impregnatedwith 10 nm silver nanoparticles took on average 22 s to open whereasit took 10 s of laser exposure using 18 nm nanoparticles [133].Interestingly, the combination of the two nanoparticle sizes incapsules shells decreased the laser exposure requirements to 5 s orless [133]. Antimicrobial and self-healing coatings are great candi-dates for light sensitization with silver nanoparticles [134].

3.3. Gold nanoparticles

Like silver nanoparticles, gold nanoparticles absorb light predom-inantly in the visible range, at around 520 nm. It is also known,however, that changing the surface properties, shape, size, syntheticapproach and the distance between neighboring gold particles canaffect the absorption spectra of gold nanoparticles. In general, theseeffects comewith a red-shift in themain plasmon absorption region ofthe nanoparticles or in the apparition of a second absorption region atlonger wavelengths. The possibility of tuning the main absorptionregion of gold nanoparticles significantly increases the versatility ofthe laser/nanoparticle interaction and consequently makes it possibleto get the most out of the gold nanoparticles as a visible light andnear-IR sensitizer for microcontainers.

The effects of modulated near-IR pulses (1064 nm) wereinvestigated using an average intensity of 30–700 mJ cm−2 per pulseto simultaneously damagemultiple polymeric microcapsules contain-ing one or more layer of densely packed gold nanoparticles [72,135].While it was demonstrated that many capsules could be damaged bycontinuous irradiation, this remote release approach has rather largeenergy requirements despite the presence of nanoparticles. Morerecently, amodulated IR sourcewas used to openmulti-compartment,“shell-in-shell” capsules [37]. Fig. 3.2 illustrates a shell-in-shellcontainer designed by coating CaCO3 particles with polyelectrolytesand gold nanoparticles (inner capsule), followed by precipitating aCaCO3 shell around the former and coating the whole with polyelec-trolytes (outer capsule). After the dissolution of the inorganic CaCO3

matrices, the inner, light sensitive polymeric container is encapsulatedwithin a larger polymer capsule.

Using an 840 nm near-IR pulsed laser, it was possible to open theinner container and release its content into the larger container [136].At the low radiant power used (10 µJ/pulse), the outer shell, whichcontained no light sensitive particles, could not be opened in controlexperiments. De Geest et al. made light responsive hybrid capsulesthat could be destroyed by laser irradiation using CaCO3 as a sacrificialtemplate [137]. Microcapsules constructed using mesoporous CaCO3

as a template are known to possess rather thick walls and areconsequently assumed to be mechanically more stable than shellsbuilt from “smooth” templates (MF, PS, and SiO2), which typicallypossess thin shells. Wu et al. used gold nanoshells to remotely releasethe content from liposomes using pulsed IR light [138]. Theincorporation of nanoparticles in the capsule wall was recentlyshown to have a beneficial impact on the mechanical stability ofmicrocapsules [44], but this effect tends to be outweighed by theeffects of wall thickness which have a greater influence on the shell'srelative stability [31,44,45].


Concerns with regards to the destructive use of pulsed lasers toremotely open polymer microcapsules were raised in Section 2.1.Unlike UV laser ablation, a photochemical process in which energeticphotons disrupt molecular bonds, the effects of IR ablation are due tothermal processes [75]. Pola et al. have conducted several investiga-tions on the decomposition of various bulk polymers by IR laserablation [139–143]. However, laser irradiation in liquids also involvesmolecular collisions of the irradiated material with the solvent whichcan deactivate the excited molecule. The shell of multilayeredpolymeric capsules containing metallic nanoparticles is partiallyhydrated and contains molecular interactions absent in bulk polymermaking IR ablation events even more complex and less likely to occur[144,145]. With regards to the presence of gold nanoparticles in thecapsule wall, Volkov et al. recently investigated the theoretical energytransfer of colloidal gold in water when irradiated with laser pulses[146]. Their results show that at high energy density, irradiating goldnanoparticles in water can result in exceeding the critical temperatureof water (Tc=647 K) with the explosive formation of vapor bubbles.This effect is accompanied by significant pressure and temperatureincrement that exponentially decays with distance from the nano-particle surface. The effects of IR ablation on living tissues have beenthoroughly reviewed by Vogel and Venugopalan [75].

These effects also support the observations made by the groups ofCaruso and Möhwald by which release of material by pulsed IRirradiation from gold functionalized capsules occurs, at least partially,due to the laser/nanoparticle interaction [37,72,135,136]. Still, thereare no reports on the mechanico-chemical effects of pulsed lasers onpolymeric microcapsules. Therefore, it cannot be excluded that theobserved release may be partially due to laser ablation, independentlyfrom the gold nanoparticles within the shell. It would be necessary toelucidate whether remote release of encapsulated substances is trulyan effect only due to the presence of nanoparticles in the aforemen-tioned experiments, for instance by using the same microcapsuledesigns as Angelatos et al. [135] or Kreft et al. [37] but impregnatingthem with a low surface coverage of gold nanorods [128] ornanoassemblies of gold nanoparticles [147], both ofwhich have strongintrinsic absorption in near-IR, instead of a densely packed shell of goldnanoparticles. If the opening observed in the aforementioned reportsis only due to the laser/plasmon heat contribution, one couldtheoretically expect that the presence of a single gold nanorod ornanoassembly per capsule should be sufficient to open the capsules(covered in Sections 3.4 and 3.5, respectively). Yet, using CWirradiation is still preferable for remote release applications thatrequire greater control over permeability in a non-destructivemanner.

3.4. Gold nanoparticles aggregates

In order to significantly reduce the irradiation intensity require-ments for optical release from polymeric microcapsules and obtainmore sensitive films with controllable properties, emphasis must beput on the organization of the films. Carefully selected thin filmdesigns could allow one to control the wall permeability and replacecurrent destructive approaches to optically address microcontainerswith reversible encapsulation and release protocols, as illustrated inFig. 3.1 [127]. Controlling the distribution of gold nanoparticles is oneof these methods by which clusters or aggregates of nanoparticleshave properties that differ from single nanoparticles in two aspects:(1) nanoparticle assemblies tend to absorb light at longer wave-lengths than their individual entities [147–149], (2) the surface areaof nanoparticle assemblies is much greater than of single nanopar-ticles [127,147]. Lu et al. also devised a method to reverse theaggregation of gold nanoparticles along with the infrared absorptionof gold aggregates being reversed [148]. However, controlling thedistribution of nanoparticles in solution while maintaining stableoptical properties is not a simple task. To obtain some degree ofcontrolled interaction between nanoparticles one must bring the

nanoparticle close enough for their electronic shells to interact andstabilize in this manner while preventing that the whole system goesuncontrolled forming very large aggregates. Polyelectrolytes can beused for this purpose [150,151]. Skirtach et al. observed that opticalproperties and stability of different types of gold nanoparticles (core–shell and DMAP-stabilized) in presence of oppositely chargedpolyelectrolytes greatly vary. After the addition of a proper polyelec-trolyte to a solution of gold nanoparticles, clusters of gold nanopar-ticles form. The aggregation of nanoparticles can be stopped alongwith the corresponding changes in absorption spectra, by transferringthe solution of growing gold complexes to a suspension of LbL coatedmicroparticles to which the aggregates adhere, stopping theirgrowths. This method referred to as “arrested aggregation” providesa convenient way to visualize the assembly behavior of nanoparticlessince the particles do not detach from the LbL coating [147]. Increasedsensitivity to near-IR irradiation was observed in gold-doped micro-capsules templated on CaCO3 microparticles [132]. This effect wasattributed to the porous nature of CaCO3 which favors interactionsbetween neighboring gold nanoparticles, influencing their absorp-tion at longer wavelengths. Bédard et al. recently demonstrated theadvantageous optical properties of assemblies of gold nanoparticlesand their use to sensitize microcapsules to near-IR irradiation(Fig. 3.3) [147]. In this case, aggregation of the nanoparticles wasobtained by adding an aliquot of citrate stabilized gold nanoparticlesinto a stirring aliquot of salt solution. A change in color from red toblue–gray resulted within seconds as single nanoparticles formdimers, and dimmers join single nanoparticles or other dimers tolarger aggregates. Volodkin et al. recently used a similar strategy toopen liposome/nanoparticle assemblies [152].

Mixing growing nanoparticle assemblies with microcapsulesallows controlling the average size of the assemblies and thus, theirmain absorption region. Two types of capsules containing the sameencapsulated molecule and differing only in the distribution of thegold nanoparticles in their shell were subjected to laser irradiation:only the ones with assemblies of nanoparticles released their content[147]. This is because, as previously explained, singly distributednanoparticles do not absorb significantly in the IR region, but in theproximity of other nanoparticles the plasmon interacts and couplesproducing an absorbance band at longer wavelengths [149]. Theoret-ical simulations revealed that in small aggregates at low laserintensity, the average temperature increase around the nanoparticlescould easily reach 10 K against less than 1 K for a single particle [147].A few Kelvin may appear insignificant but at room temperature, 10–15 K is sufficient to raise the temperature of a (PDADMAC/PSS)npolymer shell from ambient temperature to above the glass transitionof the polymer complex (Tg~37 °C for the molecular weight ofpolymers used in this study) [29]. It is believed that upon exceedingthis glass transition the shell area surrounding the nanoparticlessoftens due to a local increase in polymer entropy, which in turn leadsto the diffusion of encapsulated substances down its concentrationgradient. Using this approach, one can both minimize the amount ofnanoparticle and significantly decrease the laser intensity requiredneeded to release encapsulated substances from polymeric capsules.

3.5. Gold nanorods

Skirtach et al. recently reported on milder approaches to lightaddressable nanoparticles using gold nanorods [127,128]. Thesynthesis and optical properties of nanorods are described in greatdetails in the literature [153–156]. Like gold nanoparticles, goldnanorods absorb light, but the mean absorbance region of nanorods issituated in the near-IR region. As for colloidal gold particles, thisabsorption peak is largely dependent on surface properties, butadditionally in the case of nanorods; on their length to width ratio (i.e.aspect ratio). Selecting the synthetic conditions, one can produce goldnanorods with the dimensions that correspond to a specific

Fig. 3.3. Release of encapsulated material using a CW near-IR laser diode. Capsules impregnated with homodispersed nanoparticles before (A) and after (B) laser irradiation did notrelease their cargo (C). Capsules impregnated with aggregates of nanoparticles before (D) and after (E) irradiation released their cargo. The threshold intensity at which 50% of themicrocapsules released their content was approximately 40 mW. From [147]. Reprinted with permission of AAAS.


absorption window. Gold nanorods differ from the assemblies ofnanoparticles in the same two aspects as assemblies differ from singlenanoparticles: (1) their molar absorptivity in the near-IR is greater,and (2) the surface coverage of gold nanorods is much lower thanaggregates of gold and are instead comparable to homodistributedgold nanoparticles. These two points are particularly important if onewishes to obtain a controlled response that can be precisely tuned.

Fig. 3.4. Schematic of remote release from microcapsules containing aggregates of gold nancontaining gold nanorods (bottom row) support the theory that under mild laser-induced hpolymer matrix around them, opening a pore. Switching off the laser allows for the melted v

Just as discussed at the end of the previous section, the key tocontrol permeability with great precision and minimal irradiationintensity is not the quantity of nanoparticles used but in themagnitude of their absorption in the IR region (i.e. large molarabsorptivity). During irradiation, one locally melts the polymercomplexes around the nanorods, lowering the density of the matrixand increasing the permeability of the heated region (Fig. 3.4).

oparticles or gold nanorods (top row). The partial release observed for microcapsuleseating, the nanoparticles produce just enough heat to locally melt a small volume of theolume to cool down sealing this pore. From [127]. Reprinted with permission of AAAS.


Because gold nanorods of similar proportions possess a very narrowabsorption region in comparison with nanoparticle aggregates, therange of laser intensity needed to open “pores” in the capsules shouldbe comparatively narrow. The IR laser power range where goldaggregate-functionalized capsules could be opened spans 50 mWbecause the aggregates' size distribution in a shell is broad and largeraggregates absorb more IR than smaller ones [147]. In addition, thesmall size of nanorods leads to the opening of small pores duringirradiation of the microcapsules. Roughly identical in size, these poreswould be significantly smaller than holes created from the destructiveopening methods and definitely smaller than the pores created byaggregates of nanoparticles. The direct consequence of smaller poresis themuch lower diffusion coefficient for a substance to permeate themembrane. As a result, gold nanorods are a great candidate sensitizingmaterial to optically control the permeability of thin membranes.Skirtach et al. recently demonstrated for the first time that capsulescould be resealed after pore opening, partially releasing their contentduring the process [127]. Repeating this a second time, it was possibleto release a fraction of the capsule's cargo. In this case, resealing is theresult of the heated pore area of the capsule membrane cooling belowthe glass transition (Fig. 3.4, top panel). Nanorods also displayinteresting self-assembly possibilities that modify their optical andelectronic properties [157]. In summary, the small size and strongabsorption of gold nanorods makes it possible for shells impregnatedwith them to partially release encapsulated content during illumina-tions with an IR laser.

To summarize Section 3, various metal nanoparticles can be usedin composite polymeric microcapsules to yield interesting lightaddressable release properties. TiO2 nanoparticles offer an option todamage capsules chemically using UV, while silver and goldnanoparticles induce similar responses thermally using visible light.Incorporating aggregates of metal nanoparticles in capsules improvesthe latter's absorption at longer wavelengths, which in combinationwith inherent localization effects can be used to open “large” pores incapsules at much lower laser intensities than necessary for micro-capsules functionalized with non-aggregated nanoparticles. Goldnanorods on the other hand, offer even higher absorption in thenear-IR than aggregates of gold nanoparticles without localizationeffects, thus enabling opening “small” pores with well defined sizes inthe microcapsule wall.

4. Functional dyes for remote capsule activation

Dyes are colored compounds that absorb or emit light in the visiblerange. Those which emit do so in various manners includingphosphorescence and fluorescence. Functional dyes are those mole-cules that display properties beyond color [158]. Photochromic dyes,such as reversacol for instance, reorganize and become colored orchange color only when exposed to light. Photocatalysts such aschlorophyll-type molecules or materials found in photovoltaic cells

Fig. 4.1. Tetrasulfonated porphyrin (l

lower the activation barrier of certain reactions when irradiated at theproper wavelength. These optically addressable functionalities andmany others could be harvested to introduce new properties to thinfilms. Many functional dyes are designed to possess a high opticalstability (i.e. fastness) making them all the more suitable for lightaddressable applications. With their versatility as a whole, stability andsmall size, it is hoped that composite films of dyes and polyelectrolytesoffer a more precise approach to optically control the properties of thinfilms. The effects of laser irradiation on capsules containing fluorescentand functional dyes are discussed in this section.

4.1. Fluorescent dyes

Fluorescent dyes are regularly used to visualize polymeric micro-capsules. However, it is difficult to obtain shells with monomeric dyesas building blocks since they tend to neutralize rather than reverse theelectrostatic overcompensation that drives the LbL assembly. For thisreason, fluorescent labels may be inserted in the polymeric shells intheir monomeric form after capsule preparation [44,73], or covalentlybound onto a polymer constituent of the shells [159,160]. Alternativesto organic dyes for visualization of microcapsules are inorganicfluorophores such as quantum dots [74,161–163].

The effects of photobleaching light sensitive molecules within LbLmicrocapsules have been briefly investigated [73]. A fluorescent near-IR dye (IR 806) was absorbed on the surface of in PAH/PSS basedmicrocapsules. The shells were found to become severely damaged ordeformed when irradiated with CW near-IR at moderate intensity(830 nm, 60 mW) while capsules containing no IR 806 remainedunaffected by the laser. Although these results are encouraging anduseful as a proof of concept, the use of a simple fluorescent dye todamage microcapsules comes at the cost of photobleaching the dye,which is both irreversible and constitutes a source of activedegradation products such as radicals, which are not desirable formany applications (e.g. drug delivery) and are reminiscent of thearguments used concerning the limitations of pulsed UV laser sources(Section 2.1).

4.2. Porphyrinoid dyes

Porphyrin and phthalocyanine dyes are members of the largergroup of porphyrinoid conjugated cyclic systems of methine groups,which contain 4 and 8 aza (−N=) groups within the ring system,respectively [86]. The structure of two water-soluble dyes, porphyrintetrasulphonate and phthalocyanine tetrasulphonate are illustrated inFig. 4.1. Porphyrins are related to the largest group of naturallyoccurring dyes (chlorophyll) and have strong absorbance regionsbetween 400–500 nm. At the opposite side of the visible spectrum, asub-class of synthetic functional dyes named phthalocyaninespossesses a primary absorption peak (Q band) between 650–730 nm. Both in nature and in technological applications,

eft) and phthalocyanine (right).


porphyrinoids have the ability to lower the energy of important redoxreactions, acting as photocatalysts. The optical activity of mostporphyrins and phthalocyanines are highly concentration dependentas they tend to aggregate in aqueous solution [164–166]. Theaggregation state of porphyrins could also be controlled in solutionby light [166] and within LbL films by adjusting the pH [167]. Thesynthesis, optical properties and applications of films containingporphyrin and phthalocyanine dyes has been reviewed [168–171].The broad spectroscopic, catalytic and self-assembly properties ofporphyrin-type dyes makes them an interesting substance tofunctionalize LbL capsules and perhaps, induce optical responseswith very low energy requirements.

A method to incorporate reasonable quantities of a porphyrin dyeand induce its catalytic properties was recently reported, where anon-metallic tetrasulfonated porphyrin was incorporated in PAH/PSSmicroshells [172]. In order to significantly increase the amount ofporphyrin in the multilayer complex, the dye was premixed with theoppositely charged polycation PAH before adding the resultingmixture to PSS coated templates. This premixing strategy resulted ina fivefold increase in porphyrin content on flat substrates incomparison to adding the dye on PAH coated substrates alone.However, premixing was not advantageous when using a strongpolyelectrolyte such as PDADMAC and very little porphyrin seemed toform polyion complexes, presumably because the interaction with theoppositely charged polyelectrolyte was much more favorable thanwith the dye molecule [172]. The optical response to the dye was lessthan anticipated as damages due to the laser illumination were onlyobserved in presence of an oxidizer (15% hydrogen peroxide). Otherdyes are currently under investigation to further improve opticalresponse of shells containing photodynamic agents. While it wasdemonstrated in Section 3 that nanoparticles are most appropriate totrigger an optical response in polymeric microcapsules, metallicnanoparticles induce highly energetic and very rapid changes to themicrocapsule wall nonetheless. These can be undesirable for materialsthat are thermally sensitive (e.g. proteins) and that cannot handlelarge concentration of a release material (e.g. drugs). Controlling thepermeability of microcapsules using dyes (by driving an opticallyaddressable pH change within the shell for example) consists in apromising strategy to obtain sustained release of encapsulatedmaterials which has not been possible so far by the other meansdiscussed in the previous sections.

5. Light addressable microcapsules for cell studies

The use of polymeric microcapsules for encapsulation and deliveryof substances to living cells and tissues is an important area ofapplication that requires the combined efforts of physicists, chemists,material scientists and biologists alike. Amongst the various micro-delivery technologies that already exist (e.g. organic micelles,inorganic shells and emulsion–emulsion capsules), polymeric micro-capsules are particularly interesting due to the versatile constructionand by their relative stability. Living organisms are very sensitive toextreme environments, and the use of an indirect activation methodto address technologies alien to living cells is most appropriate. Light,magnetism and sonochemistry are the most suitable candidates forsuch a task.

5.1. Cell studies

Polymeric shells that can be remotely opened by optical means torelease encapsulated substances are interesting materials for in vivostudies. Such systems offer a protective environment to theencapsulated material allowing the investigator to store substancesinside a living organism until the proper conditions are met to releasethe substance in question [173,174]. This is advantageous in vitrosince the cells or tissue can be given the necessary time to restore an

equilibrium state after being put in presence of capsules. In vivo,however, serious concerns arise as very little is known on the fate ofsuch complex systems. Should a system perform well the task ofrecognizing a cell, being internalized and releasing its content in theappropriate cellular compartment, the question as to what happensprecisely to the capsule construct is ill understood. Even less is knownabout the fate of such capsules in higher organisms in whichmicrocapsules are exposed to metabolic processing [175]. The beststudied system for intracellular studies was gold containing polymermicrocapsules. A brief summary on light addressable microcapsulesstudies in presence of living cells is presented here. We recommendreference [10] for a complete review on biomedical applications ofpolymeric microcapsules.

Sukhorukov et al. were the first to report on the uptake ofpolymeric capsules by cells [5,176]. Parak et al. pushed their researchfurther in this direction and studied the cellular uptake [177,178],optical release of encapsulated cargo [179] and toxicity [74] ofmicrocapsules to living cells in great details. It was shown that shellsof capsules based on PAH/PSS or PDADMAC/PSS induced no cytotoxicresponse in tumor cells. However, certain nanoparticles use tosensitize the capsules to light, such as 5 nm gold could be a toxicityconcern [180,181]. Gold nanoparticles were reported to be toxic dueto (1) aggregation [174], (2) surface chemistry [182], and (3) size[175,182]. However, Hauck et al. recently reported that PDADMAC/PSS coated gold nanorods have little or no effect on cell viability [183].

The capsules studied by the joint efforts of the Sukhorukov andParak groups were constructed from non-degradable polyelectrolytes[71,177–179,184]. For drug delivery purposes degradability is oftenrequired. This aspect of biodegradability was assessed by the group ofDe Geest in vitro [10,185] and in vivo [186]. Capsules consisting ofbiopolymers such as polysaccharides and polypeptides showed to beprone to enzymatic digestion upon internalization by cultured cells.De Koker et al. injected such microcapsules subcutaneously in miceand tissue sections taken at different time intervals allowed toinvestigate the fate of the injected capsules as a function of time [186].Initially the capsules behaved as a porous implant which becomesgradually infiltrated by inflammatory cells, emerging from the borderof the injection spot. Two weeks post injection, the injection volumewas completely infiltrated by inflammatory cells and the capsuleswere found largely deformed inside cells. Thirty days post injection,no intact capsules could be observed anymore and only debris ofbroken capsules was visible [10].

Besides release from capsules governed by enzymatic digestion ofthe polyelectrolyte shell, another remote release strategy of interest isto release active species only at specific sites or upon a specific trigger.Pioneering work on this subject has been done by Skirtach et al. whodemonstrated that polymeric capsules functionalized with goldnanoparticles could, once internalized by cultured cells, be remotelyopened by IR laser irradiation without impairing the cell viability [71].In a further study, Muñoz-Javier et al. investigated the intracellularlaser activated opening of capsules more into detail [177–179]. It wasfound that high laser powers lead to cell death while moderate laserpowers could induce release of the capsules' content into the cytosolof the cells. Fig. 5.1 shows two internalized capsules loaded withfluorescently-labeled dextran before (left) and after (right) remoteopening of the microcontainer at relatively low laser intensity. It canbe seen that the dextran spreads throughout the cytosol, but is unableto spread through the nuclear membrane.

5.2. Intracellular fates of optically released materials

This ability of polymeric microcapsules to release their payloadinto the cellular cytosol points out an important property of laseractivated capsules. In general, phagocytosed species end up in endo/lysosomal compartments where they are broken down by enzymesand, if necessary, exocytosed by the cell [184]. However, for several

Fig. 5.1. Remote release of encapsulated dextran (red) inside living cells from goldfunctionalized microcapsules using a near-IR laser at 830 nm. Before release, themicrocapsules (indicated by two arrows) are found to be undamaged and internalizedin the cell. After irradiation with the laser, the dextran was released and spreadthroughout the cytosol of the cell without penetrating the nuclear membrane. From[179]. Reprinted with permission of AAAS.


classes of drug molecules, which cannot readily permeate through thecell membrane, the aim is not only to reach the endo/lysosomes butthe cytosomal space as well. This is the case in gene therapy wherepolynucleotides such as siRNA, mRNA and DNA should be deliveredinto the cellular cytosol and should even be transported to the cell'snucleus in the case of DNA. Yet, conquering the endo/lysosomalmembrane is not that straightforward. Several strategies have beendeveloped in order to improve the release of encapsulated materialfrom the endo/lysosomes into the cellular cytosol. Common methodsinvolve using membrane-disruptive peptides, lipids or polymers, oruse the buffering capacities of polymers such as PEI to cause osmoticbursting of the endo/lysosome. These methods often suffer from lowefficiency and toxic side effects. Recently, other means involving lightirradiation such as the use of photosensitizers have been explored.The latter can accumulate in the endo/lysosomal membrane and formoxygen radicals upon light irradiation causing the endo/lysosomalmembrane to rupture. Although highly efficient these photosensiti-zers are often oxic and should be administered separately from thedrug. This could cause difficulties in an in vivo setting where theminimal dose of photosensitizing dye necessary to open the endo/lysosomal membrane without affecting other cellular activities is avery challenging task. Also these small molecular weight compoundswill drain easily from the administration spot while microparticulatedrug formulation will have a much long residence time in the tissuewhere they are administered. Taking these considerations intoaccount allows us to define some potential solutions using remotelyactivated polymeric microcapsules. Firstly, these capsules allow thesimultaneous delivery of photoactive species (e.g. gold nanoparticles)and drug molecules (i.e. encapsulated within the capsules' cavity).Moreover, due to their size an efficient targeting to phagocyting cellscan be obtained and surface functionalization of the capsule wall withspecific ligands (e.g. antibodies) is easily performed, which allows toenhance their uptake by specific tissues or cells. Wang et al. recentlyintroduced capsules loadedwith Hypocrellin B (HB), a photosensitizerused in so-called photodynamic therapy to treat diseases such assome forms of cancer and viral infections [174]. Upon exposure tolight, HB generates singlet oxygen (1O2), which is cytotoxic andinduces cell death. However, HB displays no cytotoxicity in theabsence of light irradiation. To allow the not water-soluble HB to enterliving cells, it was loaded in polymeric microcapsules by non-specificinteractions applying a solvent exchange step using ethanol as asolvent for HB. Upon incubation with living cells, the HB loaded

capsules were efficiently taken up and neither capsules nor HB loadedcapsules appeared to be cytotoxic for the cells. However, uponirradiation with 488 nm light, cell viability dropped by 70%. In this invitro setting, light addressable microcapsules showed promisingcandidates for the specific delivery of drugs molecules that need aprotective container on the way to their target cells or tissue.

6. Conclusions

Microcapsules of polymers with optically addressable propertiesare being actively investigated and much attention is being put attheir potential as drug delivery vehicles. Polymer basedmicrocapsuleswere developed and investigated mostly for near-UV response. Shellsthat contain UV chromophores sensitive to photodegradation candamage to the capsule over prolonged exposure to UV light.Incorporating TiO2 nanoparticles in the microcapsule shell is a muchmore efficient way to release encapsulated material. Microcapsulescontaining stable azobenzene chromophores, however, can be used tochange the permeability of the microshells and even encapsulatesubstances. Functional dyes such as porphyrin photocatalysts can beeffectively used to damage microcapsules upon visible light exposure.The use of more reactive phthalocyanine dyes is expected to be usefulin the development of microcapsules with slow sustained releaseupon irradiation. Silver and gold nanoparticles can be used todestructively release encapsulated materials using low energyirradiation sources due to their ability to absorb photons and convertthem to heat, affecting materials around them. However, theirradiation requirements for remote opening by IR can be significantlydecreased by modifying the distribution or shape of the nanoparticlesused to impregnate polymeric microcapsules. This is partially becausethe absorbance of gold assemblies and gold nanorods are located inthe IR instead of the visible range, thus making the heat productionmore efficient. Additionally, the heat produced by gold nanorodsresult in very small pores in the capsules that are sealed whenirradiation stops. This effect makes it possible to reversibly change thepermeability of polymer microcapsules with great sensitivity. Finally,the current accomplishments in using light addressable microcap-sules in living cells and in vivo was reviewed.

Much is still expected from polymeric microcapsules and newdevelopments on their remotely addressable properties are currentlyactively investigated. This review merely highlights the combinedefforts on the topic of light addressable microcapsules done in largepart by half-a-dozen research groups around the globe in the past fiveyears. Lately, much focus has been committed to the study of lightaddressable microcapsules in living cells and tissues. An increase incollaborationwith pharmacists, biologists andhealth professionals hassignificantly improved our understanding in this respect. However,much of the reportedwork done in presence of livingmaterial involvessynthetic parts that cannot be degraded by cells. At present,destructive strategies to release substances from microcapsules arethe norm. However, many developments are still needed in order toachieve capsule constructs possessing the degree of permeabilitycontrol needed for biomedical applications. Maximizing the functionof such containers for biomedicine requires the production ofmicrocontainers that are fully biodegradable (1) with relativelysmall diameters (2) and possessing reversible and/or selectivepermeability (3). The permeability control aspect is most challenging,requiring a precise control over the pore size and the time pores areopen across the thin capsulewall. Both of these aspects could be solvedusing small, highly light sensitive materials in low concentration suchas particle aggregates, gold nanorods or functional dyes.

Acknowledgements

MFB wishes to thank Dr. Audrée Andersen for her assistance withthe pulsed UV laser experiments and Prof. Hubert Motschmann (Uni.


Regensburg) for providing the Nd:YAG laser.We gratefully acknowledgethe 6th FP EU projects STREP NMP3-CT-2005-516922 “SelectNANO” andPICT-2006-01365 (Max-Planck Society – Argentine SeCyt) for funding.BDG thanks the FWO for a post-doctoral scholarship.

References

[1] Decher G. Science 1997;277(5330):1232–7.[2] Iler RK. J Colloid Interface Sci 1966;21:569–94.[3] Donath E, Sukhorukov GB, Caruso F, Davis SA, Mohwald H. Angew Chem Int Ed

Engl 1998;37(16):2202–5.[4] Sukhorukov GB, Donath E, Davis S, Lichtenfeld H, Caruso F, Popov VI, et al. Polym

Adv Technol 1998;9(10–11):759–67.[5] Sukhorukov G, Fery A, Mohwald H. Progr Polym Sci 2005;30(8–9):885–97.[6] Sukhorukov GB. Abstr Pap Am Chem Soc 2003;226:U474-U474.[7] SukhorukovGB, FeryA, BrumenM,MohwaldH. Phys ChemChemPhys 2004;6(16):

4078–89.[8] Chang TMS. Science 1964;146:524–5.[9] Caruso F. Colloid Chem 2003;227:145–68.

[10] De Geest BG, De Koker S, Sukhorukov GB, Kreft O, ParakWJ, Skirtach AG, et al. SoftMatter 2009;5(2):282–91.

[11] Sukhorukov GB, Rogach AL, GarstkaM, Springer S, ParakWJ,Munoz-Javier A, et al.Small 2007;3(6):944–55.

[12] De Geest BG, De Koker S, Immesoete K, Demeester J, De Smedt SC, Hennink WE.Adv Mater 2008;20(19) 3687−+.

[13] De Geest BG, McShane MJ, Demeester J, De Smedt SC, Hennink WE. J Am ChemSoc 2008;130(44):14480–2.

[14] Wang YJ, Bansal V, Zelikin AN, Caruso F. Nano Lett 2008;8(6):1741–5.[15] Zelikin AN, Li Q, Caruso F. Chem Mater 2008;20(8):2655–61.[16] Tong WJ, Gao CY, Mohwald H. Chem Mater 2005;17(18):4610–6.[17] De Geest BG, Van Camp W, Prez FEDu, De Smedt SC, Demeester J, Hennink WE.

Chem Commun 2008(2):190–2.[18] De Geest BG, Van Camp W, Du Prez FE, De Smedt SC, Demeester J, Hennink WE.

Macromol Rapid Commun 2008;29(12–13):1111–8.[19] Connal LA, Kinnane CR, Zelikin AN, Caruso F. Chem Mater 2009;21(4):576–8.[20] Ochs CJ, Such GK, Stadler B, Caruso F. Biomacromolecules 2008;9(12):3389–96.[21] Discher BM, Won YY, Ege DS, Lee JCM, Bates FS, Discher DE, et al. Science

1999;284(5417):1143–6.[22] Angelatos AS, Wang YJ, Caruso F. Langmuir 2008;24(8):4224–30.[23] Buchel G, Unger KK, Matsumoto A, Tsutsumi K. AdvMater 1998;10(13) 1036−+.[24] Tao X, Su JM. Curr Nanosci 2008;4(3):308–13.[25] Bedard M, Skirtach AG, Sukhorukov GB. Macromol Rapid Commun 2007;28(15):

1517–21.[26] DongWF, Liu SQ,Wan L,Mao GZ, Kurth DG,Mohwald H. ChemMater 2005;17(20):

4992–9.[27] Kim BS, Lebedeva OV, Koynov K, Gong HF, Glasser G, Lieberwith I, et al.

Macromolecules 2005;38(12):5214–22.[28] Dong WF, Sukhorukov GB, Mohwald H. Phys Chem Chem Phys 2003;5(14):

3003–12.[29] Kohler K, Sukhorukov GB. Adv Funct Mater 2007;17(13):2053–61.[30] Gao CY, Leporatti S, Moya S, Donath E, Mohwald H. Chem - Eur J 2003;9(4):

915–20.[31] Mueller R, Kohler K, Weinkamer R, Sukhorukov G, Fery A. Macromolecules

2005;38(23):9766–71.[32] Dejugnat C, Sukhorukov GB. Langmuir 2004;20(17):7265–9.[33] Mauser T, Dejugnat C, Sukhorukov GB. Macromol Rapid Commun 2004;25(20):

1781–5.[34] Sukhorukov GB, Antipov AA, Voigt A, Donath E, Mohwald H. Macromol Rapid

Commun 2001;22(1):44–6.[35] Shutava T, Prouty M, Kommireddy D, Lvov Y. Macromolecules 2005;38(7):

2850–8.[36] Borodina T, Markvicheva E, Kunizhev S, Moehwald H, Sukhorukov GB, Kreft O.

Macromol Rapid Commun 2007;28(18–19):1894–9.[37] Kreft O, Skirtach AG, Sukhorukov GB, Mohwald H. Adv Mater 2007;19(20):

3142–5.[38] Tong WJ, Dong WF, Gao CY, Mohwald H. J Phys Chem B 2005;109(27):

13159–65.[39] Volodkin DV, Larionova NI, Sukhorukov GB. Biomacromolecules 2004;5(5):

1962–72.[40] De Geest BG, Dejugnat C, Prevot M, Sukhorukov GB, Demeester J, De Smedt SC.

Adv Funct Mater 2007;17(4):531–7.[41] De Geest BG, Dejugnat C, Verhoeven E, Sukhorukov GB, Jonas AM, Plain J, et al.

J Control Release 2006;116(2):159–69.[42] vanDijkWolthuis WNE, Hoogeboom JAM, vanSteenbergen MJ, Tsang SKY,

Hennink WE. Macromolecules 1997;30(16):4639–45.[43] De Geest BG, Sanders NN, Sukhorukov GB, Demeester J, De Smedt SC. Chem Soc

Rev 2007;36(4):636–49.[44] Bedard MF, Munoz-Javier A, Mueller R, del Pino P, Fery A, Parak WJ, et al. Soft

Matter 2009;5(1):148–55.[45] Fery A, Weinkamer R. Polymer 2007;48(25):7221–35.[46] Lulevich VV, Radtchenko IL, Sukhorukov GB, Vinogradova OI. J Phys Chem B

2003;107(12):2735–40.[47] Lulevich VV, Radtchenko IL, Sukhorukov GB, Vinogradova OI. Macromolecules

2003;36(8):2832–7.

[48] Vinogradova OI, Andrienko D, Lulevich VV, Nordschild S, Sukhorukov GB.Macromolecules 2004;37(3):1113–7.

[49] Cordeiro AL, Coelho M, Sukhorukov GB, Dubreuil F, Mohwald H. J ColloidInterface Sci 2004;280(1):68–75.

[50] Georgieva R, Dimova R, Sukhorukov G, Ibarz G, Mohwald H. J Mater Chem2005;15(40):4301–10.

[51] Heuvingh J, Zappa M, Fery A. Langmuir 2005;21(7):3165–71.[52] Gorin DA, Portnov SA, Inozemtseva OA, Luklinska Z, Yashchenok AM, Pavlov AM,

et al. Phys Chem Chem Phys 2008;10(45):6899–905.[53] Lu ZH, ProutyMD, Guo ZH, Golub VO, Kumar CSSR, Lvov YM. Langmuir 2005;21(5):

2042–50.[54] Hu SH, Tsai CH, Liao CF, Liu DM, Chen SY. Langmuir 2008;24(20):11811–8.[55] Rivera Gil P, del Mercato LL, del-Pino P, Munoz-Javier A, Parak WJ. Nano Today

2008;3(3–4):12–21.[56] Gedanken A. Chem - Eur J 2008;14(13):3840–53.[57] Suslick KS, Hammerton DA, Cline RE. J Am Chem Soc 1986;108(18):5641–2.[58] Shchukin DG, Mohwald H. Phys Chem Chem Phys 2006;8(30):3496–506.[59] Cai WB, Chen XY. Small 2007;3(11):1840–54.[60] Meng FH, Zhong ZY, Feijen J. Biomacromolecules 2009;10(2):197–209.[61] Yu TH, Wang ZB, Mason TJ. Ultrason Sonochem 2004;11(2):95–103.[62] Prausnitz MR, Langer R. Nat Biotechnol 2008;26(11):1261–8.[63] Dalecki D. Annu Rev Biomed Eng 2004;6:229–48.[64] De Geest BG, Skirtach AG,Mamedov AA, Antipov AA, Kotov NA, De Smedt SC, et al.

Small 2007;3(5):804–8.[65] Skirtach AG, De Geest BG, Mamedov A, Antipov AA, Kotov NA, Sukhorukov GB.

J Mater Chem 2007;17(11):1050–4.[66] Shchukin DG, Gorin DA, Moehwald H. Langmuir 2006;22(17):7400–4.[67] Sukhorukov GB, Mohwald H. Trends Biotech 2007;25(3):93–8.[68] Araya E, Olmedo I, Bastus NG, Guerrero S, Puntes VF, Giralt E, et al. Nanoscale Res

Lett 2008;3(11):435–43.[69] Kogan MJ, Bastus NG, Amigo R, Grillo-Bosch D, Araya E, Turiel A, et al. Nano Lett

2006;6(1):110–5.[70] Gorin DA, Shchukin DG, Mikhailov AI, Kohler K, Sergeev SA, Portnov SA, et al.

Tech Phys Lett 2006;32(1):70–2.[71] Skirtach AG, Javier AM, Kreft O, Kohler K, Alberola AP, Mohwald H, et al. Angew

Chem Int Ed Engl 2006;45(28):4612–7.[72] Radt B, Smith TA, Caruso F. Adv Mater 2004;16(23–24):2184–9.[73] Skirtach AG, Antipov AA, Shchukin DG, Sukhorukov GB. Langmuir 2004;20(17):

6988–92.[74] Kirchner C, Javier AM, Susha AS, Rogach AL, Kreft O, Sukhorukov GB, et al. Talanta

2005;67(3):486–91.[75] Vogel A, Venugopalan V. Chem Rev 2003;103(2):577–644.[76] Zhigilei LV, Kodali PBS, Garrison BJ. J Phys Chem B 1998;102(16):2845–53.[77] Dyer PE, Srinivasan R. Appl Phys Lett 1986;48(6):445–7.[78] Ashkin A. Biophys J 1992;61(2):569–82.[79] Gauthier RC. Appl Phys Lett 1995;67(16):2269–71.[80] Grover SC, Gauthier RC, Skirtach AG. Opt Express 2000;7(13):533–9.[81] Katagiri K, Matsuda A, Caruso F. Macromolecules 2006;39(23):8067–74.[82] Kohler K, Shchukin DG, Mohwald H, Sukhorukov GB. J Phys Chem B 2005;109(39):

18250–9.[83] Kohler K, Mohwald H, Sukhorukov GB. J Phys Chem B 2006;110(47):24002–10.[84] Mauser T, Dejugnat C, Sukhorukov GB. J Phys Chem B 2006;110(41):20246–53.[85] Kohler K, Biesheuvel PM, Weinkamer R, Mohwald H, Sukhorukov GB. Phys Rev

Lett 2006;97(18).[86] Zollinger H. Color Chemistry. Syntheses, Properties, and Applications of Organic

Dyes and Pigments. 3rd ed. Switzerland: VHCA; 2006. p. 637.[87] Rau H. In: Rabek JF, editor. Photochemistry and Photophysics, vol. 2. Florida: CRC

Press, Inc.; 1990.[88] Ishii K, Hamada T, Hatakeyama M, Sugimoto R, Nagasaki T, Takagi M.

Chembiochem 2009;10(2):251–6.[89] Cao WX, Ye SJ, Cao SG, Zhao C. Macromol Rapid Commun 1997;18(11):983–9.[90] Chen JY, Huang L, Ying LM, Luo GB, Zhao XS, Cao WX. Langmuir 1999;15(21):

7208–12.[91] Chen JY, Luo H, Cao WX. Polym Int 2000;49(4):382–6.[92] Sun JQ,Wu T, Sun YP,Wang ZQ, Zhang X, Shen JC, et al. Chem Commun 1998(17):

1853–4.[93] Zhu HG, McShane MJ. Langmuir 2005;21(1):424–30.[94] Pastoriza-Santos I, Scholer B, Caruso F. Adv Funct Mater 2001;11(2):122–8.[95] Jung BD, Hong JD, Voigt A, Leporatti S, Dahne L, Donath E, et al. Colloids Surf A

Physicochem Eng Asp 2002;198:483–9.[96] Zucolotto V, Neto NMB, Rodrigues JJ, Constantino CJL, Zilio SC, Mendonca CR, et al.

J Nanosci Nanotech 2004;4(7):855–60.[97] Tao X, Li JB, Mohwald H. Chem - Eur J 2004;10(14):3397–403.[98] Suzuki I, Ishizaki T, Hoshi T, Anzai J. Macromolecules 2002;35(2):577–80.[99] Tanchak OM, Barrett CJ. Macromolecules 2005;38(25):10566–70.[100] El Halabieh RH, Mermut O, Barrett CJ. Pure Appl Chem 2004;76(7–8):1445–65.[101] Casson JL, McBranch DW, Robinson JM, Wang HL, Roberts JB, Chiarelli PA, et al.

J Phys Chem B 2000;104(50):11996–2001.[102] Chiarelli PA, Johal MS, Holmes DJ, Casson JL, Robinson JM, Wang HL. Langmuir

2002;18(1):168–73.[103] Dante S, Advincula R, Frank CW, Stroeve P. Langmuir 1999;15(1):193–201.[104] Han LH, Tang TJ, Chen S. Nanotechnology 2006;17(18):4600–5.[105] Shchukin DG, Sviridov DV. J Photochem Photobiol C Photochem Rev 2006;7(1):

23–39.[106] Shchukin DG, Ustinovich E, Sviridov DV, Lvov YM, Sukhorukov GB. Photochem

Photobiol Sci 2003;2(10):975–7.


[107] Shchukin DG, Radtchenko IL, Sukhorukov GB. ChemPhysChem 2003;4(10):1101–3.

[108] Caruso F. Adv Mater 2001;13(1):11–22.[109] Eustis S, El-Sayed MA. Chem Soc Rev 2006;35(3):209–17.[110] Govorov AO, Richardson HH. Nano Today 2007;2(1):30–8.[111] Govorov AO, ZhangW, Skeini T, Richardson H, Lee J, Kotov NA. Nanoscale Res Lett

2006;1(1):84–90.[112] Huang XH, Jain PK, El-Sayed IH, El-Sayed MA. Nanomedicine 2007;2(5):681–93.[113] Deshpande AS, Shchukin DG, Ustinovich E, Antonietti M, Caruso RA. Adv Funct

Mater 2005;15(2):239–45.[114] Li N, Kommireddy DS, Lvov Y, Liebenberg W, Tiedt LR, De Villiers MM. J Nanosci

Nanotech 2006;6(9–10):3252–60.[115] Skorb EV, Antonouskaya LI, Belyasova NA, Shchukin DG, Mohwald H, Sviridov

DV. Appl Catal B Environ 2008;84(1–2):94–9.[116] Guan HN, Chi DF, Yu JC, Li X. Pestic Biochem Physiol 2008;92(2):83–91.[117] Hu YX, Ge JP, Sun YG, Zhang TR, Yin YD. Nano Lett 2007;7(6):1832–6.[118] Katagiri K, Koumoto K, Iseya S, Sakai M, Matsuda A, Caruso F. Chem Mater

2009;21(2):195–7.[119] Bronshtein LM, Valetskii PM, Antonietti M. Vysokomol Soedin Ser A Ser B

1997;39(11):1847–55.[120] Skorb EV, Shchukin DG, Sviridov DV. Mol Nanoscale Syst Energy Convers

2008:75–86 192.[121] Leventis HC, Streeter I, Wildgoose GG, Lawrence NS, Jiang L, Jones TGJ, et al.

Talanta 2004;63(4):1039–51.[122] KimKS, Lee JY, Park BJ, Sung JH, Chin I, Choi HJ, et al. Colloid Polym Sci 2006;284(7):

813–6.[123] Verberg R, Dale AT, Kumar P, Alexeev A, Balazs AC. J R Soc Interface 2007;4(13):

349–57.[124] VolodkinD, Arntz Y, Schaaf P,MoehwaldH, Voegel JC, Ball V. SoftMatter 2008;4(1):

122–30.[125] Gao CY, Moya S, Lichtenfeld H, Casoli A, Fiedler H, Donath E, et al. Macromol

Mater Eng 2001;286(6):355–61.[126] Sukhorukov GB, Shchukin DG, Dong WF, Mohwald H, Lulevich VV, Vinogradova

OI. Macromol Chem Phys 2004;205(4):530–5.[127] Skirtach AG, Karageorgiev P, BedardMF, Sukhorukov GB, Mohwald H. J Am Chem

Soc 2008;130(35) 11572−+.[128] Skirtach AG, Karageorgiev P, De Geest BG, Pazos-Perez N, Braun D, Sukhorukov

GB. Adv Mater 2008;20(3) 506−+.[129] Skirtach A, Kreft O. In: Villiers MM, Aramwit P, Kwon GS, editors. Nanotechnol-

ogy in Drug Delivery. Springer; 2009.[130] Murphy CJ, Gole AM, Hunyadi SE, Orendorff CJ. Inorg Chem 2006;45(19):7544–54.[131] Murphy CJ, San TK, Gole AM, Orendorff CJ, Gao JX, Gou L, et al. J Phys Chem B

2005;109(29):13857–70.[132] Bukreeva TV, Parakhonsky BV, Skirtach AG, Susha AS, Sukhorukov GB. Crystallogr

Rep 2006;51(5):863–9.[133] Radziuk D, Shchukin DG, Skirtach A, Mohwald H, Sukhorukov G. Langmuir

2007;23(8):4612–7.[134] Malcher M, Volodkin D, Heurtault B, Andre P, Schaaf P, Mohwald H, et al.

Langmuir 2008;24(18):10209–15.[135] Angelatos AS, Radt B, Caruso F. J Phys Chem B 2005;109(7):3071–6.[136] Kreft O, Prevot M, Mohwald H, Sukhorukov GB. Angew Chem Int Ed Engl

2007;46(29):5605–8.[137] De Geest BG, Skirtach AG, De Beer TRM, Sukhorukov GB, Bracke L, Baeyens WRG,

et al. Macromol Rapid Commun 2007;28(1):88–95.[138] Wu GH, Milkhailovsky A, Khant HA, Fu C, Chiu W, Zasadzinski JA. J Am Chem Soc

2008;130(26) 8175−+.[139] Blazevska-Gilev J, Bastl Z, Subrt J, Stopka P, Pola J. PolymDegrad Stab 2009;94(2):

196–200.[140] Blazevska-Gilev J, Kupcik J, Subrt J, Bastl Z, Vorlicek V, Galikova A, et al. Polym

Degrad Stab 2006;91(2):213–20.[141] Kupcik J, Blazevska-Gilev J, Subrt J, Vorkicek V, Pola J. Polym Degrad Stab

2006;91(11):2560–6.[142] Pola J, Kupcik J, Blechta V, Galikova A, Galik A, Subrt J, et al. Chem Mater

2002;14(3):1242–8.[143] Pola J, Kupcik J, Durani SMA, Khavaja EE, Masoudi HM, Bastl Z, et al. Chem Mater

2003;15(20):3887–93.[144] Kugler R, Schmitt J, Knoll W. Macromol Chem Phys 2002;203(2):413–9.[145] Dejugnat C, Kohler K, Dubois M, Sukhorukov GB, Mohwald H, Zemb T, et al. Adv

Mater 2007;19(10):1331–6.

[146] Volkov AN, Sevilla C, Zhigilei LV. Appl Surf Sci 2007;253(15):6394–9.[147] Bedard MF, Braun D, Sukhorukov GB, Skirtach AG. ACS Nano 2008;2(9):1807–16.[148] Lu C, Mohwald H, Fery A. J Phys Chem C 2007;111(27):10082–7.[149] Shipway AN, Lahav M, Gabai R, Willner I. Langmuir 2000;16(23):8789–95.[150] Bronshtein LM, Valetskii PM, Antonietti M. Vysokomol Soedin Ser A Ser B

1997;39(11):1847–55.[151] Skirtach AG, Dejugnat C, Braun D, Susha AS, Rogach AL, Sukhorukov GB. J Phys

Chem C 2007;111(2):555–64.[152] Volodkin DV, Skirtach AG, Mohwald H. Angew Chem Int Ed Engl 2009;48(10):

1807–9.[153] Alekseeva AV, Bogatyrev VA, Khlebtsov BN, Mel'nikov AG, Dykman LA, Khlebtsov

NG. Colloid J 2006;68(6):661–78.[154] Perez-Juste J, Pastoriza-Santos I, Liz-Marzan LM, Mulvaney P. Coord Chem Rev

2005;249(17–18):1870–901.[155] Zweifel DA, Wei A. Chem Mater 2005;17(16):4256–61.[156] JiangXC, BrioudeA, PileniMP. Colloids SurfAPhysicochemEngAsp2006;277(1–3):

201–6.[157] Fava D, Nie Z, Winnik MA, Kumacheva E. Adv Mater 2008;20(22):4318–22.[158] Kim S-H. Functional Dyes. Amsterdam: Elsevier; 2006.[159] Caruso F, Lichtenfeld H, Donath E, Mohwald H. Macromolecules 1999;32(7):

2317–28.[160] Dai ZF, Voigt A, Leporatti S, DonathE,Dahne L,MohwaldH.AdvMater 2001;13(17):

1339–42.[161] Gaponik N, Radtchenko IL, Gerstenberger MR, Fedutik YA, Sukhorukov GB,

Rogach AL. Nano Lett 2003;3(3):369–72.[162] Jamieson T, Bakhshi R, Petrova D, Pocock R, Imani M, Seifalian AM. Biomaterials

2007;28(31):4717–32.[163] Sharrna P, Brown S, Walter G, Santra S, Moudgil B. Adv Colloid Interface Sci

2006;123:471–85.[164] Gasyna Z, Kobayashi N, Stillman MJ. J Chem Soc Dalton Trans 1989(12):

2397–405.[165] Schwab AD, Smith DE, Rich CS, Young ER, Smith WF, de Paula JC. J Phys Chem B

2003;107(41):11339–45.[166] Wang ZC, Medforth CJ, Shelnutt JA. J Am Chem Soc 2004;126(51):16720–1.[167] Egawa Y, Hayashida R, Anzai JI. Langmuir 2007;23(26):13146–50.[168] Carballo RR, Orto VC, Hurst JA, Spiaggi A, Bonazzola C, Rezzano IN. Electrochim

Acta 2008;53(16):5215–9.[169] de la Torre G, Vazquez P, Agullo-Lopez F, Torres T. J Mater Chem 1998;8(8):

1671–83.[170] Peumans P, Yakimov A, Forrest SR. J Appl Phys 2003;93(7):3693–723.[171] Valli L. Adv Colloid Interface Sci 2005;116(1–3):13–44.[172] Bedard MF, Sadasivan S, Sukhorukov GB, Skirtach AG. J Mater Chem

2009;19:2226–33.[173] Tong WJ, Gao CY. J Mater Chem 2008;18(32):3799–812.[174] Wang KW, He Q, Yan XH, Cui Y, Qi W, Duan L, et al. J Mater Chem 2007;17

(38):4018–21.[175] Fischer HC, Chan WCW. Curr Opin Biotechnol 2007;18(6):565–71.[176] Skirtach AG, Dejugnat C, Braun D, Susha AS, Rogach AL, Parak WJ, et al. Nano Lett

2005;5(7):1371–7.[177] Javier AM, Kreft O, Alberola AP, Kirchner C, Zebli B, Susha AS, et al. Small 2006;2

(3):394–400.[178] Javier AM, Kreft O, Semmling M, Kempter S, Skirtach AG, Bruns OT, et al. Adv

Mater 2008;20(22):4281–7.[179] Javier AM, del Pino P, Bedard MF, Ho D, Skirtach AG, Sukhorukov GB, et al.

Langmuir 2008;24(21):12517–20.[180] Bhattacharya R, Mukherjee P, Xiong Z, Atala A, Soker S, Mukhopadhyay D. Nano

Lett 2004;4(12):2479–81.[181] Bhattacharya R, Patra CR, Verma R, Kumar S, Greipp PR, Mukherjee P. Adv Mater

2007;19(5) 711−+.[182] Wang SG, Lu WT, Tovmachenko O, Rai US, Yu HT, Ray PC. Chem Phys Lett

2008;463(1–3):145–9.[183] Hauck TS, Ghazani AA, Chan WCW. Small 2008;4(1):153–9.[184] Kreft O, Javier AM, Sukhorukov GB, ParakWJ. J Mater Chem 2007;17(42):4471–6.[185] De Geest BG, Vandenbroucke RE, Guenther AM, Sukhorukov GB, Hennink WE,

Sanders NN, et al. Adv Mater 2006;18(8):1005–9.[186] De Koker S, De Geest BG, Cuvelier C, Ferdinande L, Deckers W, Hennink WE, et al.

Adv Funct Mater 2007;17(18):3754–63.

Polymeric Microcapsules With Ligth Responsive Properties for Encapsulation and Release

Documents

Transcript of Polymeric Microcapsules With Ligth Responsive Properties for Encapsulation and Release