Volta

Biodegradable Mn-LDH-Ce6 potentiates cGas-STING pathway activation through sonodynamic-propelled pyroptosis for synergistic tumor immunotherapy

While immunotherapy represents a breakthrough in cancer treatment by enabling specific tumor targeting with reduced toxicity, its success is often impeded by the immunosuppressive tumor microenvironment (TME). Conditions within the TME, particularly hypoxia and high glutathione (GSH) concentrations, actively suppress immune activation, leading to suboptimal therapeutic outcomes. To address these limitations, we developed a manganese-doped layered double hydroxide nanosystem loaded with chlorin e6 (Mn-LDH-Ce6). By catalyzing the decomposition of endogenous H 2 O 2 into oxygen, the platform’s catalase (CAT)-mimetic function enhances the sonodynamic therapy under ultrasound. This synergistically results in a pronounced increase in ROS and oxidative stress, while the subsequent irradiation further propagates ROS generation and directly initiates pyroptosis. However, the elevated glutathione levels in the TME paradoxically …

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