Gold-embedded yolk-shell mesoporous organosilica nanocomposite for microwave-enhanced targeted chemotherapy and immune modulation in hepatocellular carcinoma

Microwave ablation (MWA), an innovative therapy for hepatocellular carcinoma (HCC), faces challenges of limited thermal effects and a tumor immunosuppressive microenvironment. Addressing these, we developed an advanced Au@PMO@DOX-Lac nanocomposite, aimed at enhancing the microwave thermal effect, while simultaneously facilitating targeted chemotherapy and immunomodulation. This nanocomposite, incorporating gold-embedded yolk-shell mesoporous organosilica nanoparticles, amplifies microwave thermal effects from two aspects: molecular hotspots created at the gold-silica interface and the confinement effect within its hollow nanostructure. These enhancements facilitate more effective tumor ablation with reduced microwave power requirements and shorter treatment durations. Additionally, surface modification with lactobionic acid and loading with doxorubicin allow the nanocomposite to perform precise, targeted synergistic chemotherapy. After ablation, the nanocomposite increased cytotoxic T cells and reduced regulatory T cells, while shifting macrophages from the immunosuppressive M2 to the anti-tumor M1 phenotype, significantly enhancing localized and systemic anti-tumor immune responses. Overall, this multifunctional nanocomposite not only overcomes the thermal limitations of MWA but also addresses the tumor's immunosuppressive environment, providing a promising approach for treating HCC and potentially other cancers with similar therapeutic challenges.