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 Ca_(3)(PO_(4))_(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.