Engineered Bio‐Heterojunction for Effective Treatment of Colorectal Cancer Through Intratumoral Bacteria Scavenging and Autophagy Regulation

Abstract Intratumor bacteria, a critical component of the tumor microenvironment, can facilitate tumor growth and contribute to the development of resistance to chemotherapeutic agents. The agents not only induce protective autophagy in tumors, contributing to drug resistance, but also exert minimal effects on bacteria within the tumor, thereby potentially accelerating tumor recurrence. To address this tough issue, vermiculite/copper telluride bio‐heterojunctions (VIC bio‐HJs) have been developed to enhance tumor autophagy and eradicate bacteria within the tumor to obtain a victory in the fight against tumors. VIC bio‐HJs are able to generate substantial reactive oxygen species (ROS) via photodynamic/chemodynamic therapy, effectively eliminating bacteria within the tumor by disrupting bacterial integrity and impairing electron transport chains. Concurrently, increased production of ROS leads to decreased mitochondrial membrane potential and apoptosis in tumor cells. In vivo assays and sequencing analysis confirm that VIC bio‐HJs have excellent bacteria‐killing ability while being able to induce excessive autophagy in tumor cells, ultimately leading to more cell death. Such work proposes a strategy for designing bio‐heterojunctions capable of tumor eradication and bacteria removal, offering a promising approach to improve the efficacy of bacterial‐infiltrated tumor therapy.