In vitro &in vivo targeting behaviors of biotinylated Pluronic F127/poly(lactic acid) nanoparticles through biotin–avidin interaction

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.