Interfacially Mineralized Magnetic Colloidal Gel with Microenvironment-Triggered Disassembly for Interventional Treatment of Hepatocellular Carcinoma.

Abstract

Colloidal gels (CGs) are attractive carriers for functional nanoparticles (NPs) in biomedical applications. However, the current interfacial design of CG networks often lacks efficient disassembly mechanisms, resulting in limited intelligent responsiveness, constraining their advancements in precision medicine. Herein, we developed an interfacial mineralization strategy to fabricate a mineralized magnetic colloidal gel (MMG) tailored for disassembling in the acidic tumor microenvironment. MMG comprises electrostatically attracted mineralized magnetic core-shell Fe3O4@calcium phosphate (CaP) NPs and gelatin NPs, exhibiting outstanding injectability and magnetic-heating effect, and presenting potential for minimally invasive interventional therapy of tumors. Benefiting from the dissolution of the interfacial CaP layer in an acidic microenvironment, the storage modulus of MMG decreased from 1400 to 400 Pa after 48 h, while the drug-release efficiency increased from ∼35% to ∼70%. In comparison, the unmineralized magnetic CG showed few changes in mechanical properties and exhibited a low drug-release efficiency of ∼20%. The acid-triggered disassembly of MMG's network confirmed the feasibility of precision chemotherapy. Additionally, MMG-mediated magnetic hyperthermia and chemotherapy significantly improved a synergistic therapeutic effect in tumor-bearing mice and ultrasound-guided interventional hepatic tumor rabbits. These findings demonstrate that the interfacial mineralization strategy provides an innovative approach to imparting CG's network with microenvironment-responsive controllable disassembly behavior.