Acid‐sensitive reactive oxygen species triggered dual‐drug delivery systems for chemo‐photodynamic therapy to overcome multidrug resistance. Issue 7 (18th March 2020) - Yin, Liping
Abstract: In clinical treatment, multidrug resistance (MDR) is one of the major obstacles resulting in the failure of chemotherapy. It is still a challenge to overcome MDR. Herein, we fabricated intelligent dextran‐based dual‐drug delivery systems histidine modified dextran conjugated doxorubicin/zinc porphyrin/paclitaxel (DHTD/Zn‐TPP/PTX) via supramolecular metallo‐coordination for synergistic chemo‐photodynamic therapy to overcome cancer drug resistance. In this designed DHTD/Zn‐TPP/PTX, one anticancer drug (doxorubicin, DOX) was conjugated on the dextran backbone through a reactive oxygen species sensitive linker and the other drug PTX was encapsulated into the acid responsive supramolecular micelles formed by the photosensitizer Zn‐TPP and histidine grafted on dextran. DHTD/Zn‐TPP/PTX with excellent stability could be effectively internalized by tumour cells. In the acidic tumour environment, the loaded PTX and Zn‐TPP as photosensitizer could be released; moreover, when irradiated with light the conjugated DOX could be specifically released because the linker broke. As the obtained data indicate, DHTD/Zn‐TPP/PTX exhibited not only an enhanced anticancer therapeutic effect but also significant growth inhibition for drug‐resistant MCF‐7/ADR cells to reverse MDR, having great potential for synergistic treatments of cancer to overcome MDR. © 2020 Society of Chemical Industry Abstract : An intelligent dual‐drug delivery system (DHT/Zn‐TPP/PTX) was constructed via supramolecular metallo‐coordination for synergistic chemo‐photodynamic therapy to overcome cancer drug resistance.