Biomineralized CO gas-releasing nanoprodrug for endoplasmic reticulum stress mediated cancer therapy

The anti-tumor effect of therapeutic carbon monoxide (CO) has been considered concerning the electron transport chain on the inner mitochondrial membrane. Herein, a tumor microenvironment and photo-responsive CO nanoplatform Ca-Flav nanoparticles (NPs) were constructed through biomineralizing acryloyl-modified flavonol, which could release CO both in normoxia and hypoxia conditions upon irradiation at tumor lesion. The in vitro experiments demonstrated that the endoplasmic reticulum stress-related signal pathways could be activated through oxidative stress caused by CO mediated mitochondrial biogenesis and calcium ion turbulence induced by Ca₃(PO₄)₂ acidolysis, resulting in mitochondrial dysfunction and cell apoptosis. In addition, the Ca-Flav NPs exhibited excellent biocompatibility and tumor inhibition effect in vivo. This work provides new insight into the potential characteristics of CO, paving a new way to engineer more efficient treatment based on CO.