Overcome the Doxorubicin Resistance by Moltimodal Nanoparticles in Mice

The efficacy of many chemotherapeutic agents is reduced in cells that have developed multiple drug resistance (MDR). To address this important problem, a biodegradable polymer was coupled to the photosensitizer and the resulting photosensitizer-nanoparticles were loaded with the chemotherapeutic agent doxorubicin. The combination of photosensitizer and chemotherapeutic agent had a synergistic action on a doxorubicin-resistant breast cancer MCF-7 cells. To increase the effectiveness of this combination, D-alpha-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS), an inhibitor of the multidrug transporter overproduced in these resistant cells, was added during the formation of the nanoparticles. Clearly, the tumor regrowth delay was observed after administration of doxorubicin-loaded photosensitizer-nanoparticles plus light. This combination of photodynamic activity in a powerful nanocarrier loaded with the chemotherapeutic agent doxorubicin can be used to deliver two types of cancer therapy simultaneously and can overcome the drug resistance in vivo. Therefore, this innovative delivery system can act as a potential nanomedicine for both drugsensitive and drug-resistant cancer therapy.