A MOF-Lanthanide Theranostic Agent with Bidirectional Near-Infrared Photon Conversion for Tumor-Responsive Therapy and Real-Time Imaging

Smart tumor-responsive theranostic agents are crucial for advancing precision medicine by enabling targeted drug delivery with minimal off-target effects and allowing real-time monitoring of therapeutic outcomes. Although metal-organic frameworks (MOFs) hold promises as nanocarriers, they often lack integrated, stimuli-responsive imaging and therapeutic capabilities. Here, we present a multifunctional MOF-lanthanide theranostic agent featuring bidirectional near-infrared (NIR) photon conversion for image-guided, tumor-specific therapy. The MOF carrier MIL-53(Fe) encapsulates curcumin, a natural photosensitizer and chemotherapeutic agent, which is selectively released in the acidic tumor microenvironment via pH-triggered framework degradation. This degradation also releases Fe³⁺ ions, initiating Fenton reactions to produce hydroxyl radicals for chemodynamic therapy (CDT). Lanthanide nanoparticles, satellited on the MOF, enable NIR-to-visible/ultraviolet upconversion to activate curcumin for photodynamic therapy (PDT), as well as NIR-to-NIR II (∼1530 nm) downshifting emission for deep-tissue imaging <i>in vivo</i>. Notably, the NIR II luminescence, initially quenched by metallic node ions (Fe³⁺) in MOF, is restored during MOF degradation, allowing semi-quantitative visualization of drug release. <i>In vivo</i> NIR-II imaging demonstrates peak tumor accumulation of the agent at 24 h postinjection and near-complete systemic clearance by day 14. This platform achieves a synergistic chemotherapy/CDT/PDT effect, with about 80% cell-killing efficiency and a 15-fold tumor inhibition compared to controls, highlighting its potential as an efficient theragnostic agent for precision oncology.