Acid-responsive dextran-based therapeutic nanoplatforms for photodynamic-chemotherapy against multidrug resistance

Abstract

Limited by multidrug resistance (MDR) and nonspecific selectivity, free molecular chemotherapies still are inefficient in clinical cancer treatment. Nanoscale therapeutics delivery systems with controllable release capacity have been developed to reverse multidrug resistance and improve anticancer efficacy. Herein, we constructed acid-sensitive dextrin-based nanoplatforms (THDP) to deliver chemotherapies via supramolecular coordination between tetra sodium meso-tetra (sulfonatophenyl)-porphyrin zinc (II) (Zn-TPPS) and histidine modified dextrin-graft-poly (ethylene glycol) (HDP) to reverse multidrug resistance through photodynamic-chemotherapy. The introductions of hydrophilic poly (ethylene glycol) (PEG) not only prevent undesired aggregation under physiological conditions but also enhanced cellular endocytosis effect. Doxorubicin loaded nanoplatforms (THDP@DOX) with a relatively uniform size of average 63 nm exhibited excellent stability in blood circulation. When THDP@DOX was internalized, the acidic intercellular environment could control the chemotherapies release. Moreover, the generated reactive oxygen species by photosensitizer Zn-TPPS with light irradiation could obviously block DOX efflux and ultimately induce apoptosis to effectively reverse multidrug resistance of tumor cells. Meanwhile, the combination of photosensitizers and chemotherapies obviously created an enhanced MDR reversal effect, providing a promising approach for MDR reversal to achieve highly efficient cancer therapeutics.