DACHPt-Loaded Unimolecular Micelles Based on Hydrophilic Dendritic Block Copolymers for Enhanced Therapy of Lung Cancer
2017
Liu, Gan | Gao, Hongjun | Zuo, Yixiong | Zeng, Xiaowei | Tao, Wei | Tsai, Hsiang-i | Mei, Lin
Combining sufficient stability during circulation and desirable drug release is still a great challenge for the clinical applications of nanocarriers. To satisfy this demand, we developed a novel unimolecular micelle (UM) to deliver the antitumor agent 1,2-diaminocyclohexane-platinum(II) (DACHPt) for enhanced therapy of lung cancer. This DACHPt-loaded UM (UM/DACHPt) was formed through chelate complexation between DACHPt and a hydrophilic and biodegradable dendritic block copolymer poly(amidoamine)-polyglutamic acid-b-polyethylene glycol (PAM-PGlu-b-PEG), which was composed of generation 3 PAMAM (PAMAM-G3), polyglutamic acid, and long-circulating polymer PEG. This UM/DACHPt displayed robust stability and would effectively inhibit the undesired release under physiological condition, thus exhibiting much longer in vivo half-life than diblock copolymer micelles. With significant in vitro cell cytotoxicity to A549 lung cancer cells, this UM/DACHPt demonstrated efficient antitumor efficacy on an A549 xenograft tumor model with negligible tissue cytotocxity. Therefore, this UM/DACHPt provides a promising new strategy for lung cancer therapy.
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