title: Smart nanocarrier based on PEGylated hyaluronic acid for cancer therapy.
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.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Choi
authors.forename: Hong Yeol
authors.initials: HY
authors.lastname: Yoon
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Sang Mun
authors.initials: SM
authors.lastname: Bae
authors.forename: Rang-Woon
authors.initials: RW
authors.lastname: Park
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport; D002166:Camptothecin / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011092:Polyethylene Glycols; D004317:Doxorubicin; D006820:Hyaluronic Acid; D002166:Camptothecin