Choi, Ki Young Yoon, Hong Yeol Kim, Jong-Ho Bae, Sang Mun Park, Rang-Woon Kang, Young Mo Kim, In-San Kwon, Ick Chan Choi, Kuiwon Jeong, Seo Young Kim, Kwangmeyung Park, Jae Hyung 2024-01-20T16:02:52Z 2024-01-20T16:02:52Z 2021-09-04 2011-11 1936-0851 https://pubs.kist.re.kr/handle/201004/129859 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 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. English AMER CHEMICAL SOC INTRACELLULAR DRUG-DELIVERY BLOCK-COPOLYMER MICELLES ANTITUMOR EFFICACY PROSTATE-CANCER TUMOR-CELLS PH NANOTECHNOLOGY EXPRESSION POLYMER CD44 Smart Nanocarrier Based on PEGylated Hyaluronic Acid for Cancer Therapy Article 10.1021/nn202070n 1 ACS NANO, v.5, no.11, pp.8591 - 8599 ACS NANO 5 11 8591 8599 scie scopus 000297143300016 2-s2.0-81855226471 Chemistry, Multidisciplinary Chemistry, Physical Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article INTRACELLULAR DRUG-DELIVERY BLOCK-COPOLYMER MICELLES ANTITUMOR EFFICACY PROSTATE-CANCER TUMOR-CELLS PH NANOTECHNOLOGY EXPRESSION POLYMER CD44 hyaluronic acid nanoparticle Hyal-1 camptothecin drug release tumor targeting