Chemotherapy/anti-inflammatory drug co-delivery system based on ortho ester-modified pluronic L61 for reversing tumor multidrug resistance
Journal of Drug Delivery Science and Technology(2024)
摘要
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-OEL61/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 antiinflammatory 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.
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关键词
Ortho ester,Pluronic,Multidrug resistance,Synergistic effect,Sulindac
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