Long Circulating Self-Assembled Nanoparticles from Cholesterol-Containing Brush-Like Block Copolymers for Improved Drug Delivery to Tumors

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• 作者：Thanh-Huyen Tran ; Chi Thanh Nguyen ; Laura Gonzalez-Fajardo ; Derek Hargrove ; Donghui Song ; Prashant Deshmukh ; Lalit Mahajan ; Dennis Ndaya ; Laijun Lai ; Rajeswari M. Kasi ; Xiuling Lu
• 刊名：Biomacromolecules
• 出版年：2014
• 出版时间：November 10, 2014
• 年：2014
• 卷：15
• 期：11
• 页码：4363-4375
• 全文大小：732K
• ISSN：1526-4602

文摘

Amphiphilic brush-like block copolymers composed of polynorbonene-cholesterol/poly(ethylene glycol) (P(NBCh9-b-NBPEG)) self-assembled to form a long circulating nanostructure capable of encapsulating the anticancer drug doxorubicin (DOX) with high drug loading (22.1% w/w). The release of DOX from the DOX-loaded P(NBCh9-b-NBPEG) nanoparticles (DOX-NPs) was steady at less than 2% per day in PBS. DOX-NPs were effectively internalized by human cervical cancer cells (HeLa) and showed dose-dependent cytotoxicity, whereas blank nanoparticles were noncytotoxic. The DOX-NPs demonstrated a superior in vivo circulation time relative to that of free DOX. Tissue distribution and in vivo imaging studies showed that DOX-NPs preferentially accumulated in tumor tissue with markedly reduced accumulation in the heart and other vital organs. The DOX-NPs greatly improved survival and significantly inhibited tumor growth in tumor-bearing SCID mice compared to that for the untreated and free DOX-treated groups. The results indicated that self-assembled P(NBCh9-b-NBPEG) may be a useful carrier for improving tumor delivery of hydrophobic anticancer drugs.