title: Photo-crosslinked hyaluronic acid nanoparticles with improved stability for in vivo tumor-targeted drug delivery.
abstract: One of the major hurdles of the nanoparticles as drug carriers is the unintended burst release of loaded drugs during blood circulation. To surmount this issue, we developed photo-crosslinked hyaluronic acid nanoparticles (c-HANPs) with improved stability for tumor-targeted drug delivery. They were readily prepared via UV-triggered chemical crosslinking with the acrylate groups in the polymer backbone. The size of c-HANPs was not much different from that of uncrosslinked HANPs. However, c-HANPs exhibited significantly high stability in a physiological buffer and released the loaded drug, paclitaxel (PTX), in a sustained manner. It is noteworthy that the drug release rate from c-HANPs remarkably increased in the presence of hyaluronidase, an enzyme abundant at the intracellular compartments of the tumor cells. It was found from in vitro cellular uptake tests that c-HANPs were rapidly taken up by the tumor cells via the receptor (CD44)-mediated endocytosis, which was not inhibited by photo-crosslinking. In non-invasive animal imaging results, they showed higher tumor-targeting ability than uncrosslinked HANPs because high stability of c-HANPs enabled their long circulation in the body. Owing to the sustained release of the drug and enhanced tumor-targeting ability, c-HANPs showed higher therapeutic efficacy compared to free PTX and uncrosslinked HANPs. These data implied the promising potential of c-HANP as tumor-targeting drug carriers and demonstrated the remarkable effect of the improved stability upon the biodistribution and therapeutic efficacy of drug-loaded nanoparticles.
authors.affiliation: Center for Theragnosis, Korea Institute of Science and Technology, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Hong Yeol
authors.initials: HY
authors.lastname: Yoon
authors.forename: Heebeom
authors.initials: H
authors.lastname: Koo
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Choi
authors.forename: Ick
authors.initials: I
authors.lastname: Chan Kwon
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006820:Hyaluronic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000648:ultrastructure; D008027:Light; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D010316:Particle Size; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D003432:Cross-Linking Reagents; D006820:Hyaluronic Acid; D017239:Paclitaxel