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

Abstract

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). Herein, a multifunctional nanoplatform was engineered to modulate the tumor microenvironment for highly efficient SDT. In this system, sonosensitizers and catalase were encapsulated in disulfide-bridged mesoporous organosilicon nanoparticles with high loading, which protected the activity of catalase and ensure the stability of sonosensitizers and enzyme. Subsequently hyaluronic acid was grafted onto the nanoplatform to reeducate TAMs and induce the secretion of exogenous hydrogen peroxide. Due to the good protection of enzyme, the catalase within the nanoplatform efficiently produced the mount of O 2 through decomposing the H 2 O 2 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. Based on the multiple adjustments to tumor microenvironment, our nanoplatform displayed extraordinary sonodynamic therapeutic effect with low systemic toxicity.