A high-valence bismuth(V) nanoplatform triggers cancer cell death and anti-tumor immune responses with exogenous excitation-free endogenous H₂O₂- and O₂-independent ROS generation.

Abstract

Reactive oxygen species with evoked immunotherapy holds tremendous promise for cancer treatment but has limitations due to its dependence on exogenous excitation and/or endogenous H₂O₂ and O₂. Here we report a versatile oxidizing pentavalent bismuth(V) nanoplatform (NaBi^VO₃-PEG) can generate reactive oxygen species in an excitation-free and H₂O₂- and O₂-independent manner. Upon exposure to the tumor microenvironment, NaBi^VO₃-PEG undergoes continuous H⁺-accelerated hydrolysis with •OH and ¹O₂ generation through electron transfer-mediated Bi^V-to-Bi^III conversion and lattice oxygen transformation. The simultaneous release of sodium counterions after endocytosis triggers caspase-1-mediated pyroptosis. NaBi^VO₃-PEG intratumorally administered initiates robust therapeutic efficacies against both primary and distant tumors and activates systemic immune responses to combat tumor metastasis. NaBi^VO₃-PEG intravenously administered can efficiently accumulate at the tumor site for further real-time computed tomography monitoring, immunotherapy, or alternative synergistic immune-radiotherapy. Overall, this work offers a nanomedicine based on high-valence bismuth(V) nanoplatform and underscores its great potential for cancer immunotherapy.