Preparation of paclitaxel long-circulating nanomicelles and their multidrug resistance to breast cancer

ObjectiveTo prepare paclitaxel long-circulating micelle TPGS-PEG2000-DSPE-PTX and investigate the effects of paclitaxel micelles on proliferation, apoptosis, migration and invasion of paclitaxel-resistant cells (MCF-7/PR) in breast cancer.

MethodsThe paclitaxel-loaded TPGS-PEG2000-DSPE-PTX micelles were prepared by membrane dispersion method.The morphology, particle size and potential of the drug-loaded micelles were characterized..The sulfonyl rhodamine B method, flow cytometry and migration were performed.Sulfonylrhodamine B staining, Annexin V/PI staining, scratch and transwell assays were used to detect the effects of paclitaxel micelles on proliferation, apoptosis, migration, and invasion of paclitaxel resistant cell lines.

ResultsPaclitaxel-loaded micelles were successfully constructed.The results of transmission electron microscopy showed that the drug-loaded micelles became spherical, with a particle size of 30-40 nm and a zeta potential of -5.4 mV.The UV spectrophotometer detected and calculated the drug loading amount to 25.37%.Compared with the control group and the paclitaxel group, the TPGS-PEG2000-DSPE-PTX group effectively inhibited the proliferation, migration and invasion of drug-resistant cells, induced apoptosis, up-regulated the protein expression levels of caspase3 and Bax(P < 0.01), and down-regulated Bcl-2, P-gp and MRP protein expression levels(P < 0.01).

ConclusionsThe successful construction of TPGS modified paclitaxel long-circulating micelle delivery system can effectively exert anti-tumor effect and reverse multi-drug resistance in vitro, and provide a reference for the development of a new anti-cancer drug delivery system.