Biodegradable Nanosonosensitizers with the Multiple Modulation of Tumor Microenvironment for Enhanced Sonodynamic Therapy

BACKGROUND: The specific microenvironment of solid tumors, which is characterized by hypoxia, overexpression of glutathione (GSH), and high accumulation of anti-inflammatory tumor-associated macrophages (TAMs), limits the efficiency of sonodynamic therapy (SDT). METHOD AND RESULTS: through decomposing the hydrogen peroxide in tumor tissues, which remarkably alleviated tumor hypoxia. Furthermore, degradation of the nanoparticles was observed in response to GSH, which effectively decreased the intracellular GSH level, further favoring SDT-triggered anticancer effect. CONCLUSION: Based on the multiple adjustments to tumor microenvironment, our nanoplatform displayed extraordinary sonodynamic therapeutic effect with low systemic toxicity.