Smart Nanocarrier Based on PEGylated Hyaluronic Acid for Cancer Therapy

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• 作者：Ki Young Choi ; Hong Yeol Yoon ; Jong-Ho Kim ; Sang Mun Bae ; Rang-Woon Park ; Young Mo Kang ; In-San Kim ; Ick Chan Kwon ; Kuiwon Choi ; Seo Young Jeong ; Kwangmeyung Kim ; Jae Hyung Park
• 刊名：ACS Nano
• 出版年：2011
• 出版时间：November 22, 2011
• 年：2011
• 卷：5
• 期：11
• 页码：8591-8599
• 全文大小：1145K
• 年卷期：0
• ISSN：1936-086X

文摘

Tumor targetability and site-specific drug release of therapeutic nanoparticles are key factors for effective cancer therapy. In this study, poly(ethylene glycol) (PEG)-conjugated hyaluronic acid nanoparticles (P-HA-NPs) were investigated as carriers for anticancer drugs including doxorubicin and camptothecin (CPT). P-HA-NPs were internalized into cancer cells (SCC7 and MDA-MB-231) via receptor-mediated endocytosis, but were rarely taken up by normal fibroblasts (NIH-3T3). During in vitro drug release tests, P-HA-NPs rapidly released drugs when incubated with cancer cells, extracts of tumor tissues, or the enzyme Hyal-1, which is abundant in the intracellular compartments of cancer cells. CPT-loaded P-HA-NPs (CPT-P-HA-NPs) showed dose-dependent cytotoxicity to cancer cells (MDA-MB-231, SCC7, and HCT 116) and significantly lower cytotoxicity against normal fibroblasts (NIH-3T3) than free CPT. Unexpectedly, high concentrations of CPT-P-HA-NPs demonstrated greater cytotoxicity to cancer cells than free CPT. An in vivo biodistribution study indicated that P-HA-NPs selectively accumulated into tumor sites after systemic administration into tumor-bearing mice, primarily due to prolonged circulation in the blood and binding to a receptor (CD44) that was overexpressed on the cancer cells. In addition, when CPT-P-HA-NPs were systemically administrated into tumor-bearing mice, we saw no significant increases in tumor size for at least 35 days, implying high antitumor activity. Overall, P-HA-NPs showed promising potential as a drug carrier for cancer therapy.