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-PICT3). To achieve NIR-PICT3, 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-PICT3 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.