An engineered microbial nanohybrid for enhanced photothermal-chemodynamic therapy through controlled gas generation

Photothermal enhanced chemodynamic therapy (CDT) has been recognized as an effective synergistic therapy because photothermal effect can accelerate the generation of hydroxyl radicals through promoting the Fenton reaction efficacy. However, the therapeutic effect is still challenged by upregulation of heat shock protein (HSP) expression and insufficient hydrogen peroxide in the tumor microenvironment. Herein, we report an engineered microbial nanohybrid to address these obstacles through controlled hydrogen sulfide (H₂S) gas generation. The microbial nanohybrid MG1655-yham-PdPt is constructed by combining temperature-activated H₂S-producing engineered Escherichia coli MG1655 with palladium and platinum nanoparticles modification. The nanoparticles exhibit photothermal property and peroxidase-like activity, thereby realizing photothermal enhanced CDT. Furthermore, high temperature can activate the overexpression of cysteine desulfurase, resulting in scale-up production of H₂S. The H₂S can not only downregulate the expression of HSP, but also increase the efficiency of Fenton-like reaction through suppressing the activity of catalase and decreasing the intracellular pH. Therefore, this study provides a promising strategy to realize gas-assisted photothermal-CDT.