In this study, a novel protein-polymer conjugate, d-α-tocopheryl polyethylene glycol succinate modified reduced bovine serum albumin (TPGS-Re-BSA, TRB), was synthesized for lipophilic anticancer drug delivery, and its unique ability to overcome drug resistance was explored. This conjugate was extensively characterized for its chemical structure, average molecular weight, secondary structure, degree of substitution, hydrophobicity, particle size and zeta potential. PTX-loaded nanoparticles (NPs) with diameters of 170-370 nm and drug loading efficiency of up to 13.62% were successfully prepared by the dialysis method. These drug-loaded NPs were found to exhibit a sustained release of PTX at pH 7.4, 6.5 and 5.5. Moreover, great anti-tumor activity in drug sensitive MCF-7 cells was observed in the in vitro anti-tumor studies. In particular, enhanced cytotoxicity and PTX-induced apoptosis were observed in the drug-resistant MCF-7/ADR cells compared to the Taxol and PTX-loaded BSA NPs. This could be attributed to the significant inhibition of P-gp activity and reduced ATP levels due to the presence of TRB NPs. Lastly, in vivo tumor inhibition assay verified the higher efficacy of TRB NPs. Overall, the results suggest that this TRB NPs could provide an effective carrier system for the delivery of anticancer agents.
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