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  • Nano Res

    1

    Multifunctional electrospinning composite fibers for

    orthotopic cancer treatment in vivo

    Yinyin Chen1,2, Shi Liu2, †, Zhiyao Hou1, Pingan Ma1, Dongmei Yang1,2, Chunxia Li 1 () and Jun

    Lin1()

    Nano Res., Just Accepted Manuscript • DOI: 10.1007/s12274-014-0701-y

    http://www.thenanoresearch.com on December 23 2014

    © Tsinghua University Press 2014

    Just Accepted

    This is a “Just Accepted” manuscript, which has been examined by the peer-review process and has been

    accepted for publication. A “Just Accepted” manuscript is published online shortly after its acceptance,

    which is prior to technical editing and formatting and author proofing. Tsinghua University Press (TUP)

    provides “Just Accepted” as an optional and free service which allows authors to make their results available

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    article. Please note that technical editing may introduce minor changes to the manuscript text and/or

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    which is identical for all formats of publication.

    Nano Research DOI 10.1007/s12274-014-0701-y

  • Multifunctional Electrospinning Composite Fibers for

    Orthotopic Cancer Treatment in Vivo

    Multifunctional Electrospinning Composite Fibers for

    Orthotopic Cancer Treatment in Vivo

    Yinyin Chen1,2, Shi Liu2, , Zhiyao Hou1, Pingan Ma1,

    Dongmei Yang1,2, Chunxia Li 1*, and Jun Lin1*

    1State Key Laboratory of Rare Earth Resource

    Utilization, Changchun Institute of Applied Chemistry,

    Chinese Academy of Sciences, Changchun 130024, P. R.

    China

    2 University of the Chinese Academy of Sciences Beijing

    100049, P.R. China

    State Key Laboratory of Polymer Physics and Chemistry,

    Changchun Institute of Applied Chemistry, Chinese

    Academy of Sciences

    A multifunctional dual drug carrier platform

    DOX-NaGdF4:Yb/Er@NaGdF4:Yb@mSiO2-PEG@MC-PG was

    successfully assembled via electrospinning process. The resultant

    multifunctional spinning pieces can be implanted directly to the tumor

    site of mice by surgical procedures to fulfill the orthotopic

    chemotherapy by the controlled release of DOX from mesoporous

    SiO2 and the upconversion fluorescence/magnetic resonance dual

    model imaging through NaGdF4:Yb/Er@NaGdF4:Yb embedded in

    MC/UCNPS/DOX in vivo.

  • Multifunctional Electrospinning Composite Fibers for

    Orthotopic Cancer Treatment in Vivo

    Yinyin Chen1,2, Shi Liu2, †, Zhiyao Hou1, Pingan Ma1, Dongmei Yang1,2, Chunxia Li 1 () and Jun Lin1()

    Received: day month year

    Revised: day month year

    Accepted: day month year

    (automatically inserted by

    the publisher)

    © Tsinghua University Press

    and Springer-Verlag Berlin

    Heidelberg 2014

    KEYWORDS

    Electrospinning

    Orthotopic, Treatment,

    Controlled Release,

    Multiple Structure

    ABSTRACT

    A multifunctional dual drug carrier platform was successfully assembled. The

    antitumor drug doxorubicin (DOX) loaded core-shell structured

    NaGdF4:Yb/Er@NaGdF4:Yb@mSiO2-polyethylene glycol (abbreviated as UCNPS)

    nanoparticles were incorporated into antiphlogistic drug indomethacin (MC)

    loaded poly(ε-caprolactone) (PCL) and galatin to form nanofibrous fabrics (labeled

    as MC/UCNPS/DOX) via electrospinning process. The resultant multifunctional

    spinning pieces can be implanted directly to the tumor site of mice by surgical

    procedures to fulfill the orthotopic chemotherapy by the controlled release of DOX

    from mesoporous SiO2 and the upconversion fluorescence/magnetic resonance dual

    model imaging through NaGdF4:Yb/Er@NaGdF4:Yb embedded in

    MC/UCNPS/DOX in vivo.

    1. Introduction

    Both unresectable tumors for example hepatocellular

    carcinoma and metastases cancer such as breast

    cancer, renal carcinoma, lung cancer and so on

    represent a major clinical problem owing to the poor

    prognosis. There are about 50–80% of patients

    experiencing recurrence by 5 years after resection,

    partly resulting from invisible intrahepatic

    Nano Research DOI (automatically inserted by the publisher)

    Review Article/Research Article Please choose one

    Address correspondence to Jun Lin. jlin@ciac.ac.cn; Chunxia Li. cxli@ciac.ac.cn

  • | www.editorialmanager.com/nare/default.asp

    2 Nano Res.

    metastases during resection [1]. For the treatment of

    unresectable cancer or for the prevention of

    post-surgery tumor recurrence, chemotherapy will be

    a good choice. The nonspecific systematic

    distribution of the antitumor drugs is one of the main

    disadvantages of the conventional tumor

    chemotherapy [2-4]. In this case, orthotopic treatment

    is an inevitable and promising approach. Although

    many targeting therapeutic strategies have been

    developed, due to the difficulty to transport

    effectively the chemotherapy drugs to the specific

    location in the context of multiple in vivo

    physiological barriers [5, 6], the management of

    malignant cancers still remains clinical challenge.

    Thus, it will be necessary to prolong blood

    circulation of antitumor drug. Owing to the excellent

    character of mesoporous SiO2, such as good

    biocompatibility, large specific surface area, tunable

    mesoporous structure, and facile surface

    functionalization and so on, it has recently acted as a

    potential anticancer therapy, from which the

    prolonged drug release with tunable drug release

    kinetics could be achieved. Moreover, mesoporous

    SiO2 could enhance the dissolution of the poorly

    water-soluble drugs and increase their bioavailability,

    and mesoporous SiO2 with small sizes preferably

    accumulate at tumor sites caused by the enhanced

    permeability and retention (EPR) effect [7, 8].

    Electrospinning is a cutting edge technology for

    producing continuous polymer fibers that has

    recently attracted attention in the field of drug

    delivery [9, 10]. Owing to their unique characteristics

    such as extremely high surface area and excellent

    pore interconnectivity, electrospun polymeric fibers

    are particularly attractive for carriers for a series of

    drugs and even can be engineered to smart delivery

    drug in a controlled fashion [11-16]. More importantly,

    the electrospun fibers as a kind of implant materials

    can be exploited to site-specific delivery of drugs to

    the body as well as wound healing or surgery

    treatment.

    Molecular imaging techniques, such as magnetic

  • www.theNanoResearch.com∣www.Springer.com/journal/12274 | Nano Research

    3 Nano Res.

    resonance imaging (MRI) [17, 18], X-ray computed

    tomography (CT), upconvension fluorescence

    microscopy [19-22], and positron emission tomography

    (PET) play an important role in medicine and

    biomedical research [23, 24]. The information obtained

    from single modal molecular imaging cannot satisfy

    the higher requirements on the efficiency and

    accuracy for clinical diagnosis and medical research

    [25, 26]. Thus, multimodality imaging will provide more

    complementary, effective and accurate information

    on the physical anatomical structure and the

    physiological function for diagnosis and treatment.

    Resulting from their special 4f electron structure and

    rich optical-magnetic properties [27-29],

    lanthanide-based nano-probes have attracted

    increasing attention in multimodal molecular

    imaging. In particular, due to the existence of seven

    unpaired electrons in 4f orbit of Gd3+ ions,

    upconversion nanoparticles containing Gd3+ ions can

    exhibit fluorescent and magnetic properties.

    Therefore, such nanoparticle can be regarded as a

    multimodal imaging biological probe for

    simultaneous UCL and MRI.

    So in this work, we put forward a

    multifunctional anticancer drug carrier platform, in

    which antitumor drug doxorubicin (DOX) loaded

    core-shell structured

    NaGdF4:Yb/Er@NaGdF4:Yb@mSiO2-polyethylene

    glycol (abbreviated as UCNPS) nanoparticles were

    incorporated into antiphlogistic drug indomethacin

    (MC) loaded poly(ε-caprolactone) (PCL) and galatin

    to form nanofibrous fabrics (labeled as

    MC/UCNPS/DOX) via electrospinning process. The

    resultant multifunctional spinning pieces can be

    implanted directly to the tumor site of mice by

    surg