International Journal of Nanomedicine (Apr 2021)
Biodegradable Nanosonosensitizers with the Multiple Modulation of Tumor Microenvironment for Enhanced Sonodynamic Therapy
Abstract
Hang Zhou,1,2,* Jiawei Sun,1,* Jiaqi Wu,1 Hong Wei,1 Xianli Zhou1 1In-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Ultrasound, Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, 310058, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianli ZhouIn-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of ChinaTel/Fax +86-0451-86605362Email [email protected]: 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: 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 O2 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.Keywords: sonodynamic therapy, hypoxia, tumor-associated macrophages, catalase, glutathione depletion
