Self-delivery nanomedicine to overcome drug resistance for synergistic chemotherapy†

Multidrug resistance (MDR) is one of the prime reasons for the failure of cancer chemotherapy, which continues to be a great challenge to be solved. In this work, alpha-tocopherol succinate (alpha-TOS) and doxorubicin (DOX)-based self-delivery nanomedicine (designated as alpha-TD) is prepared to combat drug resistance for cancer synergistic chemotherapy. Carrier-free alpha-TD possesses a fairly high drug loading rate and improves the cellular uptake via the endocytosis pathway. More importantly, the apoptotic inducer alpha-TOS could elevate the reactive oxygen species (ROS) generation, disrupt mitochondrial function and reduce adenosine 5 '-triphosphate (ATP) production, which facilitate the intracellular drug retention while decreasing its efflux. As a result, alpha-TD achieves a considerable synergistic chemotherapeutic effect against drug resistant cancer cells. Moreover, it also exhibits a preferable inhibitory effect on tumor growth with a low system toxicity in vivo. This synergistic drug self-delivery strategy would open a new window for developing carrier-free nanomedicine for overcoming drug resistance in cancer therapy.

Automated summary

The study developed a self-delivery nanomedicine based on alpha-TOS and DOX to combat multidrug resistance in cancer, increasing cellular uptake efficiency and enhancing intracellular drug retention. The synergistic effect of alpha-TD showed significant inhibition of drug-resistant cancer cell growth in vivo.