A Covalently Engineered Metal–Organic Framework Nanosystem for Imaging-Guided Photoimmunotherapy of Metastatic Tumors

Metastatic cancer presents a formidable clinical challenge due to the limitations of conventional therapies in addressing both primary tumors and systemic spread. Here, we developed a supramolecular nanoscale metal-organic framework platform, UIO66-IR808-POEGMA (UIP), designed to integrate multimodal imaging with potent combination therapy for systemic intervention. UIP enables simultaneous photoacoustic and fluorescence imaging, providing real-time guidance for treatment. Upon 808 nm laser irradiation, the platform mediates synergistic photodynamic and photothermal effects, leading to the effective ablation of the primary tumors. Crucially, this localized therapy induces a robust antitumor immune response. In a murine model bearing 4T1 tumors, this imaging-guided strategy completely eradicated the primary tumors and markedly suppressed the growth of distant lesions (19.8% by volume compared to the PBS group). This work demonstrates UIP as a promising integrated theranostic system for imaging-guided control of metastatic disease.