Optically-controlled bacterial metabolite for cancer therapy

• Published in: Nature communications Vol. 9; no. 1; pp. 1680 - 12
• Main Authors: Zheng, Di-Wei, Chen, Ying, Li, Zi-Hao, Xu, Lu, Li, Chu-Xin, Li, Bin, Fan, Jin-Xuan, Cheng, Si-Xue, Zhang, Xian-Zheng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.04.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 14/19; 147/143; 631/1647/2234; 639/301/54/990; 64/60; 692/699/67/1059/602; 96/34; Bacteria; Cancer; Cancer therapies; Carbon nitride; Cytotoxicity; E coli; Escherichia coli; Humanities and Social Sciences; Irradiation; Light irradiation; Microenvironments; multidisciplinary; Nitric oxide; Photoelectrons; Radiation; Science; Science (multidisciplinary); Therapy; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03233-9

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 (C 3 N 4 ) 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 C 3 N 4 can be transferred to E. coli to promote the enzymatic reduction of endogenous NO 3 – to cytotoxic NO with a 37-fold increase. In a mouse model, C 3 N 4 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. Targeting tumors with bacteria as vehicles for metabolite therapy suffers from low efficiency and robustness. Here, the authors combine carbon nitride with nitric oxide generation enzyme-positive E. coli for photo-controlled metabolite therapy (PMT) and observe increased effects both in vitro and in tumor-bearing mice.