pH-triggered "PEG" sheddable and folic acid-targeted nanoparticles for docetaxel delivery in breast cancer treatment.

Multifunctional nanoparticles have attracted significant attentions for oncology and cancer treatment. In fact, they could address critical point for tumour treatment by creating a stimuli-responsive targeted drug delivery system that can exist stably in the systemic circulation, efficiently penetrate the tumour tissue, and then accumulate in tumour cells in large quantities. A novel stepwise pH-responsive multifunctional nanoparticles (FPDPCNPs/DTX) for targeted delivery of the antitumour drug docetaxel (DTX) is prepared by coating a tumour acidity-sensitive "sheddable" FA modified β-carboxylic amide functionalized PEG layer (folic acid-polyethylene glycol-2,3-dimethylmaleic anhydride, FA-PEG-DA) on the cationic drug-loaded core (poly(β-amino ester-cholesterol, PAE-Chol) through electrostatic interaction in this study. The charge shielding behaviour of the FPDPCNPs/DTX was confirmed by zeta potential assay. The surface charges of the nanoparticles can change from positive to negative after PEG coating. The IC50 values of FPDPCNPs/DTX was 3.04 times higher than that of PEG "unsheddable" nanoparticles in cytotoxicity experiments. The results of in vivo experiment further showed that FPDPCNPs/DTX had enhanced tumour targeting effect, the tumour inhibition rate of FPDPCNPs/DTX was as high as 81.99%, which was 1.51 times that of free DTX. Under a micro acidic environment and folate receptor (FR)-mediated targeting, FPDPCNPs/DTX contributed to more uptake of DTX by MCF-7 cells. In summary, FPDPCNPs/DTX as a multifunctional nano-drug delivery system provides a promising strategy for efficiently delivering antitumour drugs.