A nano vector with photothermally enhanced drug release and retention to overcome cancer multidrug resistance

Abstract Developing a simple and effective drug delivery system for overcoming cancer multidrug resistance (MDR) is challenging. Herein, a Cu2-xSe-based photothermal vector (PT-V) with a photothermal conversion efficiency of 42.8 % was designed and synthesized to effectively deliver triphenylphosphine-modified doxorubicin (TPDOX) to mitochondria for overcoming cancer MDR. A phase change material was co-loaded to the vector to prevent drug leakage. Decorated with a folic acid group, PT-V@TPDOX was developed into a multifunctional theranostic agent. The photothermal effect brings several advantages to the PT-V. First, photothermal regulation makes TPDOX release highly controllable. Then, photothermally enhanced drug release and cellular retention are achieved in MDR cells, resulting in effective mitochondria targeting of TPDOX. Finally, photothermal therapy combined with DOX-based chemotherapy shows powerful therapeutic ability with an inhibition rate of 97.3 % against tumors with MDR. This study provides a simple and effective platform to overcome MDR with a photothermal vector.