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

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.

Personalized Bacteria Loaded with Autoantigens for the Enhancement of Tumor Immunotherapy

“…[33] Salmonella strains preferentially colonize and grow in tumor tissues, whereas they are gradually cleared in the circulation and other tissues within several days. [34,35] Under our designed system, we performed a fluorescence distribution study on Panc02 tumor-bearing mouse model to evaluate the targeting ability of EnS@PDA. Distribution differences were evaluated via the fluorescence intensity of Rhodamine B.…”

Recent advances in bacteria-mediated cancer therapy

“…It is difficult to completely eradicate a malignant melanoma with conventional treatment, owing to their inherent properties of overall aggressiveness, complexity, and heterogeneity. Shi et al (2022 ) proposed a new strategy, in which metabolic engineering labeled C. butyricum is able to ablate melanoma ( Figure 6 ). In this study, d-alanine (d-Ala), a bacteria metabolic substrate of C. butyricum , was linked to AIE photosensitizer (TPApy) through click chemistry reaction to obtain d-Ala-TPApy.…”

“…Scale bar: 10 μm. Reproduced with permission from Shi et al (2022 ). Copyright 2022, John Wiley and Sons.…”

Coating bacteria for anti-tumor therapy

“…Based on the metabolic characteristics of bacteria, Shi et al (2022) showed that the metabolism of oncolytic bacteria with synthetic photosensitizer-label could specifically clear anaerobic regions of tumors in concert with photodynamic therapy. The new functionalized lysing bacterium combined with the bio-photodynamic-immunotherapy promised minimally invasive removal of malignant melanoma, hence providing a new tool for post-operative recurrence prevention.…”