Tailor-made biotuner against colorectal tumor microenvironment to transfer harms into treasures for synergistic oncotherapy

Abstract

The endogenous tumor-specific metabolites in tumor microenvironment (TME) have emerged as powerful motivators for tumor progression. In situ transformation of these harmful substances into treasures provides an innovative strategy to revolutionize cancer therapy. Herein, a tailor-made Bac@Cu2O biotuner is ingeniously designed against the specific physiological features of colorectal cancer (CRC) for synergistic oncotherapy. The intelligent biotuner is constructed by the integration of bacteria (i.e., Eubacterium hallii (E. hallii)) and Cu2O nanoparticles via electrostatic interaction. With the instinctive E. hallii-driven tumor tropism, Bac@Cu2O could actively accumulate and colonize at the tumor sites. Subsequently, Cu2O can act as a H2S scavenger to react with CRC overexpressed H2S, resulting in the generation of CuS, which could mediate Fenton-like reaction to produce cytotoxic •OH for chemodynamic therapy (CDT). Moreover, the colonized E. hallii in TME is able to effectively metabolize detrimental lactic acid into antitumor short-chain fatty acids (SCFAs) for tumor-targeted metabolic therapy. These functions conjunctively produce a “turn-bads-to-goods” scenario for chemodynamic-metabolic synergistic CRC therapy. Such a tailor-made biological material provides a simple and powerful strategy in boosting anti-CRC efficiency without the use of cytotoxic drugs, greatly enhancing the therapeutic outcomes as well as reducing the potential side effects.