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Development of transferrin functionalized poly(ethylene glycol)/poly(lactic acid) amphiphilic block copolymeric micelles as a potential delivery system targeting brain glioma

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Abstract

The aim of present study is to conceive a biodegradable poly(ethylene glycol)–polylactide (PEG–PLA) copolymer nanoparticle which can be surface biofunctionalized with ligands via biotin–avidin interactions and used as a potential drug delivery carrier targeting to brain glioma in vivo. For this aim, a new method was employed to synthesize biotinylated PEG–PLA copolymers, i.e., esterification of PEG with biotinyl chloride followed by copolymerization of hetero-biotinylated PEG with lactide. PEG–PLA nanoparticles bearing biotin groups on surface were prepared by nanoprecipitation technique and the functional protein transferrin (Tf) were coupled to the nanoparticles by taking advantage of the strong biotin–avidin complex formation. The flow cytometer measurement demonstrated the targeting ability of the nanoparticles to tumor cells in vitro, and the fluorescence microscopy observation of brain sections from C6 glioma tumor-bearing rat model gave the intuitive proof that Tf functionalized PEG–PLA nanoparticles could penetrate into tumor in vivo.

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Abbreviations

PEG:

Poly(ethylene glycol)

PLA:

Polylactide

Tf:

Transferrin

BBB:

Blood–brain barrier

TfR:

Transferrin receptor

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

Fetal bovine serum

GPC:

Gel permeation chromatography

DLS:

Dynamic light scattering

DiI:

1,1′-Dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate

FCS:

Fetal calf serum

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Acknowledgments

This work was financially supported by China National Natural Scientific Found (50573056), Tianjin Science and Technology Committee (06YFGZSH00800).

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Authors and Affiliations

  1. School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, China

    Wei-hua Ren, Jiang Chang, Cheng-hu Yan, Xiao-min Qian, Li-xia Long, Bin He, Xu-bo Yuan, Chun-sheng Kang & Jing Sheng

  2. EA 2689, Laboratory of Physiology, Faculté de Médecine pôle recherche, IMPRT, University of Lille 2, 1 place de Verdun, 59045, Lille, France

    Jiang Chang & Didier Betbeder

  3. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China

    Chun-sheng Kang & Pei-yu Pu

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  1. Wei-hua Ren
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  2. Jiang Chang
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Corresponding authors

Correspondence to Xu-bo Yuan, Chun-sheng Kang or Didier Betbeder.

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Ren, Wh., Chang, J., Yan, Ch. et al. Development of transferrin functionalized poly(ethylene glycol)/poly(lactic acid) amphiphilic block copolymeric micelles as a potential delivery system targeting brain glioma. J Mater Sci: Mater Med 21, 2673–2681 (2010). https://doi.org/10.1007/s10856-010-4106-5

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  • DOI: https://doi.org/10.1007/s10856-010-4106-5

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