Affiliation:
1. School of Materials and Energy Southwest University Chongqing 400715 China
2. State Key Laboratory of Resource Insects Southwest University Chongqing 400715 China
3. Yibin Academy of Southwest University Yibin 644000 China
Abstract
AbstractMitochondria are core regulators of tumor cell homeostasis, and their damage has become an arresting therapeutic modality against cancer. Despite the development of many mitochondrial‐targeted pharmaceutical agents, the exploration of more powerful and multifunctional medications is still underway. Herein, oxygen vacancy‐rich BiO2‐x wrapped with CaCO3 (named BiO2‐x@CaCO3/PEG, BCP) is developed for full‐fledged attack on mitochondrial function. After endocytosis of BCP by tumor cells, the CaCO3 shell can be decomposed in the acidic lysosomal compartment, leading to immediate Ca2+ release and CO2 production in the cytoplasm. Near‐infrared irradiation enhances the adsorption of CO2 onto BiO2‐x defects, which enables highly efficient photocatalysis of CO2‐to‐CO. Meanwhile, such BiO2‐x nanosheets possess catalase‐, peroxidase‐ and oxidase‐like catalytic activities under acidic pH conditions, allowing hypoxia relief and the accumulation of diverse reactive oxygen species (ROS) in the tumor microenvironment. Ca2+ overload‐induced ion dyshomeostasis, CO‐mediated respiratory chain poisoning, ROS‐triggered oxidative stress aggravation, and cytosolic hyperoxia can cause severe mitochondrial disorders, which further lead to type I cell death in carcinoma. Not only does BCP cause irreversible apoptosis, but immunogenic cell death is simultaneously triggered to activate antitumor immunity for metastasis inhibition. Collectively, this platform promises high benefits in malignant tumor therapy and may expand the medical applications of bismuth‐based nanoagents.
Funder
National Natural Science Foundation of China
Subject
Biomaterials,Biotechnology,General Materials Science,General Chemistry