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

Abstract Self‐oxygenated phototherapy systems integrating near‐infrared fluorescence imaging (NIR FLI) and fluorine‐19 magnetic resonance imaging ( 19 F 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 F 36 NP , a dual‐modal phototherapy nanoemulsion that integrates NIR FLI, 19 F MRI, self‐oxygenated photodynamic therapy, and photothermal therapy. By rapidly pairing the photosensitizer IR780 with a fluorinated bulky counterion [Al{OC(CF 3 ) 3 } 4 ] − , F 36 IR is obtain, which is further paired with a fluorinated oil and formulated into F 36 NP . This pairing conveniently introduces sensitive 19 F MRI, effectively mitigates aggregation‐caused quenching, improves photostability and photothermal conversion efficiency. Additionally, F 36 NP facilitates oxygen delivery, alleviating tumor hypoxia and boosting photodynamic efficacy. F 36 NP 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.