Smart Nanocarrier Based on PEGylated Hyaluronic Acid for Cancer Therapy

Title
Smart Nanocarrier Based on PEGylated Hyaluronic Acid for Cancer Therapy
Authors
최귀원권익찬김광명김인산윤홍열최기영김종호배상문박라운강영모전세영박재형
Keywords
hyaluronic acid; nanoparticle; Hyal-1; camptothecin; drug release; tumor targeting
Issue Date
2011-11
Publisher
ACS Nano
Citation
VOL 5, NO 11, 8591-8599
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/59076
ISSN
19360851
Appears in Collections:
KIST Publication > Article
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