Multidrug resistance (MDR) is a primary cause of failure in oncotherapy and interest is growing in the design of multi-stimuli responsive nano-carriers to synergistically deliver chemotherapeutic agents and P-gp inhibitors to reverse MDR. The hybrid
micelles based on a
Platinum (IV)-coordinate polymeric
prodrugs and
TPGS were developed to improve
chemotherapy and reduce side effects. The pH/redox dual-sensitive
polymers were synthesized by condensation polymerization using ortho
ester monomer and diamminedichlorodisuccinatoplatinum (DSP). The hybrid
micelles possessed uniform size (38 nm) and displayed good stability in various physiological conditions. In contrast, in vitro drug release profiles indicated that these
micelles could be completely depolymerized under acidic and reducing environment, thereby more than 80 %
cisplatin were released within 12 h at pH 5.0 plus 10 mM DTT. More importantly, a large amount of
TPGS released simultaneously could effectively inhibit the function of drug efflux pumps, which significantly enhanced the cytotoxicity of
cisplatin against A549/DDP cells. The growth inhibition rate of
micelles on A549/DDP multicellular spheroids was 79.5 %, while that of free
cisplatin was only 6.8 %. Therefore, these hybrid
micelles are promising in overcoming
tumor MDR and worth doing further research in vivo and extend to other therapeutic agents.