Optically-controlled bacterial metabolite for cancer therapy

Abstract

Bacteria preferentially accumulating in tumor microenvironments can be utilized as natural vehicles for tumor targeting. However, neither current chemical nor genetic approaches alone can fully satisfy the requirements on both stability and high efficiency. Here, we propose a strategy of "charging" bacteria with a nano-photocatalyst to strengthen their metabolic activities. Carbon nitride (C₃N₄) is combined with Escherichia coli (E. coli) carrying nitric oxide (NO) generation enzymes for photo-controlled bacterial metabolite therapy (PMT). Under light irradiation, photoelectrons produced by C₃N₄ can be transferred to E. coli to promote the enzymatic reduction of endogenous NO₃^- to cytotoxic NO with a 37-fold increase. In a mouse model, C₃N₄ loaded bacteria are perfectly accumulated throughout the tumor and the PMT treatment results in around 80% inhibition of tumor growth. Thus, synthetic materials-remodeled microorganism may be used to regulate focal microenvironments and increase therapeutic efficiency.