Enabling 19F MRI and Boosting Phototherapy Through Facile Counterion Pairing of Photosensitizers

Self-oxygenated phototherapy systems integrating near-infrared fluorescence imaging (NIR FLI) and fluorine-19 magnetic resonance imaging (19F MRI) hold great promise for imaging-guided therapy of deep-seated hypoxic tumors. However, such systems are rare and often suffer from complex synthesis, suboptimal imaging and therapeutic performance. Here, a convenient and effective counterion pairing strategy is introduced to construct F36NP, a dual-modal phototherapy nanoemulsion that integrates NIR FLI, 19F MRI, self-oxygenated photodynamic therapy, and photothermal therapy. By rapidly pairing the photosensitizer IR780 with a fluorinated bulky counterion [Al{OC(CF3)3}4]−, F36IR is obtain, which is further paired with a fluorinated oil and formulated into F36NP. This pairing conveniently introduces sensitive 19F MRI, effectively mitigates aggregation-caused quenching, improves photostability and photothermal conversion efficiency. Additionally, F36NP facilitates oxygen delivery, alleviating tumor hypoxia and boosting photodynamic efficacy. F36NP exhibits efficient tumor targeting, enables multimodal imaging-guided therapy, and promotes robust reactive oxygen species generation, achieving significant tumor suppression with a low photosensitizer dose. This study demonstrates a versatile “add-on”strategy for rapidly converting a broad spectrum of cationic photosensitizers into powerful “all-in-one”dual imaging-guided phototherapy agents.