title: In vitro &in vivo targeting behaviors of biotinylated Pluronic F127/poly(lactic acid) nanoparticles through biotin-avidin interaction.
abstract: Biotinylated Pluronic F127/poly(lactic acid) block copolymers (B-F127-PLA) were successfully synthesized previously by our group. In the present study, the release behaviors of paclitaxel-loaded B-F127-PLA nanoparticles and their targeting properties to human ovarian carcinoma cells were investigated. Paclitaxel (pac) loaded in B-F127-PLA nanoparticles shows an initial burst release in the first 6h and followed by a slow release. The in vitro targeting behaviors of B-F127-PLA nanoparticles against human ovarian cancer cells (OVCAR-3, SKOV-3) were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) tests and fluorescence microscopy (FM) technique. Targeting was based on a three-step biotin-avidin targeting approach using biotinylated anti-CA125 antibody specific for the CA-125 antigen that is highly expressed on OVCAR-3 cells but not expressed on SKOV-3 cells. MTT results show that the anticancer effect of paclitaxel in B-F127-PLA nanoparticles over OVCAR-3 cells was stronger than that over SKOV-3 cells, indicating that B-F127-PLA nanoparticles were delivered more effectively to OVCAR-3 cells than to SKOV-3 cells. The targeting behaviors of B-F127-PLA nanoparticles were further confirmed by FM technique. The intracellular distribution of B-F127-PLA nanoparticles was also studied using a triple-labeling method. It was observed that B-F127-PLA nanoparticles are mainly localized within the cytoplasm of OVCAR-3 cells. The in vivo antitumor efficacy of pac-loaded B-F127-PLA nanoparticles by three-step method as measured by change in tumor volume of OVCAR-3 implanted in Balb/C nude mice was greater than that by one-step method.
authors.affiliation: School of Life Science, Jiangxi Science & Technology Normal University, Nanchang 330013, China. xyxiong@gmail.com
authors.forename: Xiang Yuan
authors.initials: XY
authors.lastname: Xiong
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.forename: Yan Chun
authors.initials: YC
authors.lastname: Gong
authors.forename: Zi Ling
authors.initials: ZL
authors.lastname: Li
authors.forename: Yu Ping
authors.initials: YP
authors.lastname: Li
authors.forename: Zhi Yong
authors.initials: ZY
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001360:Avidin / Q000008:administration & dosage / Q000378:metabolism*; D019921:Biotinylation; D018394:CA-125 Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D020442:Poloxamer / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D018394:CA-125 Antigen; D004337:Drug Carriers; D020442:Poloxamer; D001360:Avidin; D017239:Paclitaxel