Tumor pH-responsive metastable-phase manganese sulfide nanotheranostics for traceable hydrogen sulfide gas therapy primed chemodynamic therapy

Manganese-based nanomaterials have piqued great interest in cancer nanotheranostics, owing to their excellent physicochemical properties. Here we report a facile wet-chemical synthesis of size-controllable, biodegradable, and metastable gamma-phase manganese sulfide nanotheranostics, which is employed for tumor pH-responsive traceable gas therapy primed chemodynamic therapy (CDT), using bovine serum albumin (BSA) as a biological template (The final product was denoted as MnS@BSA). The as-prepared MnS@BSA can be degraded in response to the mildly acidic tumor microenvironment, releasing hydrogen sulfide (H2S) for gas therapy and manganese ions for magnetic resonance imaging (MRI) and CDT. In vitro experiments validated the pH-responsiveness of MnS@BSA at pH 6.8 and both H2S gas and center dot OH radicals were detected during its degradation. In vivo experiments showed efficiently tumor turn-on T-1-weighted MRI, significantly suppressed tumor growth and greatly prolonged survival of tumor-bearing mice following intravenous administration of MnS@BSA. Our findings indicated that MnS@BSA nanotheranostics hold great potential for traceable H2S gas therapy primed CDT of cancer.