An introduction to future drug

delivery system

By: Ali khorramdust

The prefix ‘nano’ comes from the Greek word ‘nanos’ meaning ‘a dwarf’.Hence,’nanotechnology’Might well simply mean a technology to do with ‘small’ things

Nanotechnologies are the design,characterization,production and application of structures

The size range of interest between a few nanometers and 100 nm is one where many interesting Things happen.

They can easily transferred through blood vessels and interact with targeted tumor-specificProteins both on the surface of and inside cancer cells.

Inadequate drug concentrations reaching the tumor,and the limited ability to monitor therapeutiResponses.poor drug delivery to the target site leads to significant complications.

Nanotechnology and nanomedicine has exploited the possibility of designing tumor-targetedNanocarries able to deliver radionuclide payloads in a selective manner to improve the efficacyAnd safety of cancer imaging and therapy.

The major nanocarries include nanopores,carbon nanotube,nanoparticles,dendrimers,quantumDuts,liposomes,and….

Nanotubes:Nanotubes are smaller then nanopores.

About half the diameter of a molecular of DNA also help to identify DNA changes associiatedWith cancer cells.

It helps to exactly pin point location of the changes.mutated regions associated with cancer areFirst tagged with bulky molecules.using a nano tupe tip,resembling the needle on a record playerThe physical shape of the DNA can be traced.a computer translates this information intoTopographical map.

Quantum Dotes(QD):These are tiny crystals that glow when these are stimulated by ultraviolet light.The latex beads filled with these crystals when stimulated by light,emiit the color that lights upThe sequence of interest. serving as sort of spectral bar code.

Nanotube:

Quantum Dots:

Nanoshells(NS):These are another recent invention.NS are miniscule beads coated with gold.The most useful nanoshells are those that absorb near infrared light that can easily penetrateSeveral centimeters in human tissuses.Absorption of light by nanoshells creates an intense heat that is lethal to cells.In laboratory cultures the heal generated by the light-absorbing nanoshells has successfullyKilled tumor cells while leaving neighboring cells intact.

Liposomes:Liposomes are self-assembling spherical closed colloidal structures composed of lipid bilayersThat surround a central aqueous space.Liposome based formulations of several anticancer agents have been approved for theTreatment of metastatic breast cancer and Kaposi’s sarcoma.

Liposomes:

Nanoshells:

Caltilevers:Tiny bars anchored at one end can be engineered to bind to molecules associated with cancerIt would be possible to tell whether the cancer molecules are present and hence detect earlyEvents in the development of cancer cells.

Dendrimer:A number of nanoparticles that will facilitate drug delivery are being developed.It is hoped dendrimers can be manipulated to release their contents only in the presence ofCertain trigger molecu;es associated with cancer.following drug releases the dendrimers mayAlso report bacj whether they are successfully killing their targets.

Nanopores:Nanopores(holes)allow DNA to pass through one strand at a time hence DNA sequencing canBe made more efficient.The passage of DNA through a nano pore can be used to decipher the encoded informationIncluding errors in the code known to be associated with cancer.

Cantilevers:

Dendrimers:

Nanopores:

1) Fluorescent Nanoparticles:The diagnosis and treatment of cancer have been greatly improved with the recent Developments in nanotechnology one of the promising nanoscale tools for cancer diagnosis isFluorescent nanoparticles(NPs) such as organic dye-dope NPs quantum dots and upconversionNPs that enable highly sensitive optical imaging of cancer at cellular and animal level.

2) Monoclonal antibodies and Nanobodies: In the past decades the mainstay of systemic therapy for solid and haematology malignancies Was chemotherapy nevertheless this modality has the drawbacks such as drug resistance andEliciting sever cytotoxicity in normal tissue.

The therapeutic monoclonal antibodies(mAbs) are deemed to be a class of novel agents thatCan specifically target and disrupt molecular pathways underlying tumorigenesis.the mAbs areProduced by a single clone of B-cells and are monospecific and homogeneous. The recombinant antibodies have been reduced in size rebuilt into multivalent moleculesAnd fused with different moities such as radionuclides toxins enzymes.

Focuses on implementation of the mAbs and nanobodies fragments for cancer therapy.

Recent advances in nanothechnology in cancer Treatment:

3)Nanomedicine:Nanothechnology has been extensively merging into biomedical research to develop a new Research field Nanomedicine.

The effects of gastrin messenger RNA(mRNA) down-regulation on growth of human pancreaticCancer Gastrin expression was examined in human pancreatic cancer cell lines by reverse Transcriptase-polymerase chain reaction and peptide expression was assessed by immunocytochemistery Gastrin was down-regulated using either stable transfection of an antisense gastrin cDNAOr 1 of 3 shRNA(short hairpin RNA) constructs Stable transfection in gastrin antisense or shRNAsInto BxPC-3 cells resulted in clones with more than 90% reduction in gastrin mRNA

Immunofluorescence analysis confirmed that gastrin peptide levels were decreased in antisenseAnd shRNA tumors.

4)Nanomicelles:Emerging nanotechnology has already developed various innovative nanomedicinesSelf-assemblies of block copolymers are promising nanomedicines for targeted drug delivery andImaging stimulus-responsive targeted nanomicelles are designed to release drugs on based onStimuli such as PH temperature redox potential magnetism and ultrasound.

5)Carbon Nanotubes:A vast majority of applications are based on CNTs raging from miniaturized biosensors to organRegeneration Nevertheless the complexity of biological systems poses a significant challenge inDeveloping CNT-based tissue tissue engineering applications ali khorramdust focuses on theRecent developments of CNT-based tissue engineering where the interaction between livingCells cells/tissues and the nanotubes have been transformed into a variety of novel techniques.

Functional analyses of water-dispered carbon nanohorns with antitumor activity were Performed to explore their potential as drug carrier for local cancer chemotherapy.water-Dispered carbon nanohorns were prepared by adsorption of polyethylene glycol-doxorubicinConjugate(PEG-DXR) onto oxidized single-well carbon nanohorns(oxSWNHs).PEG-DXR bound Ox SWNHs were administered intratumorally to lung cancer-cell NCI-H460-bearing mice.

In vitro studies showed that carboplatin-filled CNTs inhibited growth of bladder cacer cellsWhereas unfilled opened CNTs barely affected cancer cell growth

6)Gold Nanoparticles:Nanotechnology has used to provide advanced biomedical research tools in diagnostic imagingAnd therapy which requires targeting of nanoparticles(NPs) to individual cells and subcellularCompartments.

Results show that the cellular uptake of gold NPs is dependent on their size and surface propertyThe NPs were transported in vesicles of 300-500 nm diameter within the cytoplasm.the averageVelocity and diffusion coefficient of the vesicles containing NPs were 10.2(+/-1.8) microm/hrAnd microm 2/hr respectively Analysis of the time dependent intracellular spatial distribution ofThe NPs demonstrated that they reside in lysosomes within 40 minutes of incubation.

7)Radioprotection by nanoparticles:Radiolysis of water generates a series its radical decomposition products that inactivate Enzymes and damage cellular lipids proteins and DNA postirradiation protection is another Approach to reduce or reverse deleterious effects after exposure to ionizing radiation

Fullerenes (C60) diminished toxicity of radiation on zebra fish embryos by reducing generationOf reactive oxygen species fulleronols (C60[OH]X) protected unicellular eukaryotes organismsAgainst gamma radiation Cerium oxide nanoparticles(nanoceria) increased longevity of cells byReducing hydrogen peroxide and ultraviolet radiation induced injury Autoregerative reactionCycle Ce3+↔Ce4+ occurs on the surface of the ceria nanoparticles:changing oxidation state From Ce3+ to Ce4+ might scavenge free radicals produced by radiation.

Monitoring toxicity in real time using novel impedance technique:Interaction of mammalian cells with surfaces and focus on the kinetic aspects of thisPhenomenon is of great for science Cell attachment is an important parameter to assess cancerCell potential for metastasis and tumor healing caused by their dynamic interaction withSabstrates and drugs.

Cell-to-cell communications were studied by injecting a dye lucifer yellow to a single cellThrough a microelectrode: electrical characteristics of the cells were measured with the electrodeAnd transfer of the dye from the single cell to its neighbours by cell-to-cell gap junctions wasObserved in cell monolayers. The method that applies external electrical field to sense cellSpreading upon artificial surfaces in real time is referred to as Electric Cell-substsate ImpedenceSensing (ECIS)

Although the ECIS technique has been first described by Giaever and Keese

Measurements using ECIS of repopulation of mechanically disrupted cells in culture have beenAs well suggested as wound healing assey.

The ECIS technique is becoming a well-stablished technique to study chemical and physicalFactors and other dynamic processes.

Concentration to achieve 50% inhibition was determined in fibroblast V79 cells for free metalsAnd quantum dots: around 6µM for Cd 98µM for Zn 154nM for red CdSe/ZnS 240 nM for greenCd/ZnS. For the cadmium selenide and telluride quantum dots toxicity could be assigned to Release of free cadmium.for quantum dots and gold nanoparticles were not toxicity 200nM and45µM.

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