Synergistic nanotheranostic platform for fluorescence/magnetic resonance bimodal imaging-guided near infrared photoimmuno-chemodynamic thermal targeting therapy

Near-infrared (NIR) photoimmunotherapy (PIT) is a promising cancer treatment strategy involving antibody–photoabsorber conjugates. However, the imaging depth and photobleaching susceptibility of the IR700 fluorescence used for treatment monitoring are limited, and antigen heterogeneity within tumors compromises the efficacy of strictly antigen-restricted therapies. We developed a synergistic nanotheranostic platform that integrates NIR-PIT, photothermal therapy, and chemodynamic therapy (CDT) into a single MRI-visible agent (NIR-PICT 3 ). To achieve NIR-PICT 3 , conjugation of mAb–IRDye700DX (mAb-IR700) to dextran-coated superparamagnetic iron oxide nanoparticles (nanomag-D-spio) yielded nanomag-D-spio-mAb-IR700, enabling dual imaging (IR700 fluorescence/MRI) and targeted cytotoxicity upon 690-nm irradiation. The conjugate retained antigen selectivity, exhibited activatable NIR fluorescence after cellular uptake, generated negative T1- and T2-weighted MRI contrast, and demonstrated robust, cycle-enhanced photothermal performance. Iron-mediated redox catalysis promoted ·OH generation, supporting CDT. In vivo, systemic administration led to marked tumor accumulation, as confirmed by multimodal analyses. Repeated light dosing exploited the NIR-PIT–induced super-enhanced permeability and retention (SUPR) effect, enhancing nanoparticle retention, tumor heating, and therapeutic efficacy. In EGFR+ xenografts, NIR-PICT 3 achieved superior tumor regression and survival while inducing photothermal bystander effects in antigen-heterogeneous models. These results establish a modular, image-guided strategy for platform therapy to overcome monitoring depth limitations and antigen heterogeneity in solid tumor NIR-PIT.