MSNs-loaded HMME and Erastin-mediated ferroptosis combined with sonodynamic therapy for HCC treatment

• DOI: 10.4103/jcrt.jcrt_1531_24
• Publication Date: 2025-05-03T06:04:13Z
• Authors: Chang Zhao; Guchun Qin; Caixia Ling; Yang Zhao; Yunxi Huang; Zelong Jiang; Niqiang Zhou; Junjie Liu; Danke Su; Jinghang Jiang
• Keywords: Sonodynamic therapy

ABSTRACT Background: Ferroptosis can have a major impact on the development and advancement of hepatocellular carcinoma (HCC) due to its clear association with heightened vulnerability disease. This study aimed develop novel nanoplatform evaluate effectiveness in vivo vitro models HCC. Methods: Erastin, compound that induces iron-dependent cell death, HMME, sonosensitizer, were enclosed within mesoporous silica nanoparticles (MSNs). The engineered exhibit responsive assembly-disassembly mechanism. Hydrophilic hyaluronic acid (HA) was utilized for conjugation modification synthesize Erastin/HMME@MSNs-HA. In experiments conducted elucidate antitumor mechanisms this nanomaterial. Results: cellular experiments, Erastin/HMME@MSNs-HA rapidly degraded by hyaluronidase, leading increased endocytosis cancer cells. Cellular breakdown led generation harmful reactive oxygen species (ROS), decreased glutathione levels, lipid peroxidation, resulting decrease mitochondrial membrane potential, dysfunctional mitochondria, reduced growth, death. Additionally, nanotherapy platform, when combined ultrasound (US) treatment, exhibited significant therapeutic against tumors . It induced death cancerous tissues, tumor worsened tissue deprivation, good compatibility body. Conclusion: These findings indicate effectively alleviate hypoxia while inducing apoptosis ferroptosis, laying foundation enhancing efficacy ROS-mediated HCC therapy.