Organic radicals offer unique optoelectronic properties beyond those of conventional closed-shell materials, making them attractive candidates for advanced biomedical applications. However, their practical use is severely hindered by the intrinsic instability, and effective generation of ultrasound-responsive reactive oxygen species (ROS) with hypoxia tolerance remains largely unexplored. Here, we report a highly stable open-shell radical-based immunogenic sono/photodynamic theranostic system that enables second near-infrared (NIR-II) bioimaging and efficient tumor eradication under both light and ultrasound excitation. By employing a symmetric dual-acceptor molecular design, we develop a donor-acceptor radical (NTM-2) that exhibits a 13-fold enhancement in photodegradation resistance relative to that of the pristine radical. Upon 808 nm irradiation, NTM-2 nanoparticles simultaneously display bright NIR-II emission, pronounced photothermal conversion, and efficient type-I ROS generation. In vivo studies demonstrate high-resolution NIR-II vascular imaging and near-complete tumor ablation under photoactivation. Notably, under ultrasound stimulation, NTM-2 nanoparticles generate type-I ROS efficiently, leading to potent sonodynamic tumor suppression and significantly prolonged survival in tumor-bearing mice. This work establishes a molecular strategy for stabilizing organic radicals and highlights their potential as robust open-shell emitters for hypoxia-tolerant immunogenic sono/photodynamic cancer theranostics.
Wei et al. (Tue,) studied this question.
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