Chemotherapy/anti-inflammatory drug co-delivery system based on ortho ester-modified pluronic L61 for reversing tumor multidrug resistance

Abstract

The development of multidrug resistance (MDR) in malignant tumors is one of the major obstacles to chemotherapy. Herein, ortho ester-modified pluronic L61 (L61) was prepared and coupled with sulindac (Su) to obtain a polymeric prodrug (Su-OE-L61). Su-OE-L61 was further loaded with doxorubicin (DOX) to give a pH-sensitive nanoparticles (Su-OE-L61/DOX NPs). Compared with ortho ester-free nanoparticles (Su-L61/DOX NPs), Su-OE-L61/DOX NPs could effectively trigger drug release under tumor acidic conditions. In vitro experiments demonstrated that Su-OE-L61/DOX NPs significantly increased intracellular drug concentration and enhanced the cytotoxicity to DOX-resist cells (MCF-7/ADR) through L61-mediated anti-MDR effect and the anti-inflammatory effect of sulindac. In vivo studies revealed that the tumor inhibition rates of Su-OE-L61/DOX NPs reached 83.70 %, which was attributed to the synergistic anti-tumor effect of L61, sulindac and DOX. Overall, the chemo/anti-inflammatory drugs co-delivery system based on ortho ester-modified pluronic showed unique advantages in reversing tumor multidrug resistance.