Living Bacteria‐Based Immuno‐Photodynamic Therapy: Metabolic Labeling of Clostridium butyricum for Eradicating Malignant Melanoma

Advanced Science

Wenbo Wu¹  Leilei Shi¹  Bin Liu¹  Sha Li²  Xihui Gao²  Xiaoxiao Liu²  Yuzhen Li³ 

[1] Department of Chemical and Biomolecular Engineering National University of Singapore 4 Engineering Drive 4 Singapore 117585 Singapore;Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS) School of Basic Medical Sciences Fudan University 131 Dong An Road Shanghai 200032 China;The Eighth Affiliated Hospital Sun Yat‐Sen University 3025 Shennan Middle Road Shenzhen 518033 China;

关键词: Clostridium butyricum;    immunotherapy;    melanoma;    metabolic labeling;    photodynamic therapy;   

DOI  :  10.1002/advs.202105807

来源: DOAJ

【 摘 要 】

Abstract Due to the complexity, aggressiveness, and heterogeneity of malignant melanoma, it is difficult to eradicate the whole tumor through conventional treatment. Herein, a strategy of metabolic engineering labeled anaerobic oncolytic bacteria (Clostridium butyricum) is demonstrated to achieve the ablation of melanoma. In this system, the metabolic substrate of C. butyricum d‐alanine (d‐Ala) is first conjugated with a photosensitizer (TPApy) showing aggregation‐induced emission (AIE). The yielded metabolic substrate of d‐Ala‐TPAPy can be metabolically incorporated into bacterial peptidoglycan to form engineered C. Butyricum. Once the engineered C. butyricum is injected into melanoma, the bacteria can only proliferate in an anaerobic zone, stimulate the tumor immune microenvironment, and ablate the tumor hypoxia region. Following that, the relatively rich oxygen content in the peripheral area can induce the death of C. butyricum. The photosensitizer (PS) on the bacteria can subsequently exert a photodynamic effect in the oxygen‐rich region and further remove the melanoma residue under light irradiation. Prominent in vivo melanoma ablation results revealed that the engineering oncolytic bacteria can provide a promising regime for solid tumor eradication.

【 授权许可】

Unknown