Asymmetric N,O-Centered Stable Diradical Nanoparticles for NIR-II Fluorescence Imaging-Guided Photothermal Tumor Therapy

Abstract Stable organic radicals provide distinctive open-shell platforms for near-infrared fluorescence, but their use in NIR-II fluorescence imaging-guided photothermal therapy remains limited. Herein, we report an asymmetric N,O-centered Blatter−phenoxyl diradical (BP) and its nanoparticle formulation (BP-NPs), a water-dispersible nanoplatform prepared by encapsulating the BP by an amphiphilic polypeptide P(OEGMA)23−PLys15. BP combines the oxygen-centered phenoxy and the nitrogen-centered Blatter radical units in an asymmetric scaffold, distinguishes it from many carbon-centered radical and symmetric diradical systems, and shows an absolute photoluminescence quantum yield of 0.73%. Variable-temperature 1H NMR, high-resolution mass spectrometry, and variable-temperature EPR spectroscopy were employed to characterize the molecular structure and temperature-dependent open-shell behavior of BP. After encapsulated, the BP-NPs retained broadband visible-to-NIR absorption and NIR-II emission, with an absolute photoluminescence quantum yield of 0.41% in water. Under 808 nm irradiation, BP-NPs showed good photostability and a photothermal conversion efficiency of 27.3%. In vitro studies reveals that the BP-NPs exhibit low dark cytotoxicity but strong light-induced 4T1 cell killing, while the in vivo NIR-II imaging showed efficient tumor accumulation, with the maximum fluorescence signal and tumor-to-background ratio (TBR ≈ 9.3) observed at approximately 24 h post-injection. Photothermal therapy at this window markedly suppressed the tumor growth without obvious treatment-related body-weight loss during the observation period. This work highlights asymmetric phenoxy−Blatter N,O-centered diradical nanoparticles as promising open-shell platforms for NIR-II imaging-guided photothermal therapy.