Tumor microenvironment/NIR-responsive carbon monoxide delivery with hollow mesoporous CuS nanoparticles for MR imaging guided synergistic therapy

Abstract

The synthesis of a novel versatile nanomedicine platform integrating multiple imaging and therapeutic functions has always been a great challenge for efficient cancer diagnosis and therapy. Herein, in this study, a novel versatile carbon monoxide (CO) delivery nanoplatform was constructed with hollow mesoporous CuS NPs carrying manganese carbonyl (MnCO) to realize MR imaging-guided PTT and CO combined anticancer therapy. The MnCO@CuS nanoplatform revealed superior properties in colloidal stability, photothermal conversion, H2O2/NIR-stimulated CO release and tumoral accumulation. More importantly, the enriched H2O2 in the tumor microenvironment (TME) triggered MnCO to release CO in situ, and this process was further strengthened by the NIR irradiation. Subsequently, the intermediate products MnOx was degraded into Mn2+ by the mild acidic tumor microenvironment to enable T1-weighted MR imaging. Simultaneously, the in situ-released CO combined with NIR irradiation exhibited strongest inhibition to the growth of MV3 tumor in vitro and in vivo. Moreover, the multifunctional nanoplatform also exhibited low toxicity and good biocompatibility in vitro and in vivo. Hence, these results suggested the MnCO@CuS nanoplatform possessed significant potential in realizing TME/NIR stimulated CO/Mn2+ generation and photothermal conversion for MR imaging-guided synergistic PTT and CO anticancer therapy.

Keywords

• Carbon monoxide delivery
• Hollow mesoporous CuS NPs
• Tumor microenvironment/NIR responsiveness
• MR imaging
• Synergistic therapy