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Hyperbranched copolymer micelles as delivery vehicles of doxorubicin in breast cancer cells

Authors

  • Xianghui Zeng,

    1. Department of Neuroscience, Swedish Medical Nanoscience Center, Karolinska Institutet, Retziusväg 8, SE-171 77, Stockholm, Sweden
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  • Yuning Zhang,

    1. Department of Neuroscience, Swedish Medical Nanoscience Center, Karolinska Institutet, Retziusväg 8, SE-171 77, Stockholm, Sweden
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  • Zhihua Wu,

    1. Department of Neuroscience, Swedish Medical Nanoscience Center, Karolinska Institutet, Retziusväg 8, SE-171 77, Stockholm, Sweden
    2. State Key Laboratory of Food Science and Technology, Jiangxi-OAI Joint Research Institute, Nanchang University, No. 235 Nanjing Road East, 330047, Nanchang, China
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  • Pontus Lundberg,

    1. Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, School of Chemical Science and Engineering, Teknikringen 56-58, SE-100 44 Stockholm, Sweden
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  • Michael Malkoch,

    1. Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, School of Chemical Science and Engineering, Teknikringen 56-58, SE-100 44 Stockholm, Sweden
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  • Andreas M. Nyström

    Corresponding author
    1. Department of Neuroscience, Swedish Medical Nanoscience Center, Karolinska Institutet, Retziusväg 8, SE-171 77, Stockholm, Sweden
    • Department of Neuroscience, Swedish Medical Nanoscience Center, Karolinska Institutet, Retziusväg 8, SE-171 77, Stockholm, Sweden
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Abstract

Four types of drug nanoparticles (NPs) based on amphiphilic hyperbranched block copolymers were developed for the delivery of the chemotherapeutic doxorubicin (DOX) to breast cancer cells. These carriers have their hydrophobic interior layer composed of the hyperbranched aliphatic polyester, Boltorn® H30 or Boltorn® H40, that are polymers of poly 2,2-bis (methylol) propionic acid (bis-MPA), while the outer hydrophilic shell was composed of about 5 poly(ethylene glycol) (PEG) segments of 5 or 10 kDa molecular weight. A chemotherapeutic drug DOX, was further encapsulated in the interior of these polymer micelles and was shown to exhibit a controlled release profile. Dynamic light scattering and transmission electron microscopy analysis confirmed that the NPs were uniformly sized with a mean hydrodynamic diameter around 110 nm. DOX-loaded H30-PEG10k NPs exhibited controlled release over longer periods of time and greater cytotoxicity compared with the other materials developed against our tested breast cancer cell lines. Additionally, flow cytometry and confocal scanning laser microscopy studies indicated that the cancer cells could internalize the DOX-loaded H30-PEG10k NPs, which contributed to the sustained drug release, and induced more apoptosis than free DOX did. These findings indicate that the H30-PEG10k NPs may offer a very promising approach for delivering drugs to cancer cells. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

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