Nitric oxide-sensitized mitoxantrone chemotherapy integrated with photothermal therapy against multidrug-resistant tumors

Multidrug resistance (MDR) frequently occurs in numerous tumors treated with approved common drugs, which is often associated with the failure of chemotherapy. Therefore, treatment paradigms to reverse MDR in clinics are highly required. Herein, a versatile two-dimensional (2D) nanoplatform (N-GO-MTX-BNN6 NPs) was constructed by anchoring the chemotherapeutic drug mitoxantrone (MTX) and an NO donor (BNN6) on N-doped graphene oxide (N-GO) to fight MCF-7/ADR tumor cells. Nitric oxide (NO) was released by the regulation of UV-vis irradiation, which remarkably inhibited the expression of P-glycoprotein (transmembrane protein) and enhanced the inherent cytotoxicity of MTX by weaking the efflux of hydrophobic drugs. In addition, due to the near-infrared broad absorption of N-GO and MTX, the prepared nanoplatform exhibited an outstanding photothermal performance (η = 53.18%). Both in vitro and in vivo experiments showed that N-GO-MTX-BNN6 NPs can serve as a new approach for the treatment of multidrug-resistant tumors through NO-sensitized chemo/photothermal therapy.