Golgi-Targeted Clay Nanoregulators with Spatiotemporal Thermal Confinement and Cascade-Amplified Antigen Delivery for Tumor Therapy
Photothermal therapy (PTT) is a non-invasive tumor treatment that offers controllability, non-drug resistance, and precise ablation, yet its efficacy is limited by uncontrolled heat diffusion and weak immune responses, often leading to metastasis. Here, we report a chondroitin sulfate-modified Prussian blue-montmorillonite immunoregulator (PM@CS) that integrates tumor cell adhesion and Golgi targeting to confine photothermal damage at the organelle level. PM@CS accumulates on the Golgi apparatus, reducing heat transfer distance and enhancing photothermal ablation. This targeted hyperthermia disrupts post-translational modification and secretion of metastasis-associated proteins, with GOLPH3 and GOLM1 expression reduced by 63.4% and 70.3%, respectively. Furthermore, PM@CS promotes dendritic cell maturation (3.3-fold increase in CD80+ and CD86+ populations) and enhances antigen-specific CD4+ and CD8+ T cell proliferation, attributed to the immunoadjuvant properties of montmorillonite. Notably, PM@CS upregulates voltage-gated calcium channels (CaV) and enhances Ca2+ influx, activating calcium signaling cascades that amplify immunotherapy. This synergistic approach inhibits primary tumor growth and lung metastasis, offering a promising strategy for cancer treatment.