Spatiotemporally Controlled NIR-II Afterglow Nanoprobes via Synergistic Ultrasound and Peroxynitrite-Induced Energy Transfer for Precision Theranostics

Spatiotemporally controlled afterglow probes represent a significant advancement in remote, noninvasive disease diagnosis and therapy. However, strategies for constructing and manipulating long-wavelength afterglow probes that offer high-resolution imaging specificity and effective diagnostic and therapeutic capabilities are still rare and challenging to develop. In this study, we present a spatiotemporally controlled NIR-II afterglow nanoprobe (FZ970) for precision tumor imaging and therapy by integrating a synergistic dual-stimuli mechanism involving remotely controlled ultrasound and a tumor environment-specific peroxynitrite (ONOO^-)-induced energy transfer process. The nanoprobe is designed by coencapsulating a NIR-II afterglow substrate and sonosensitizer within a nanoparticle. Upon remote ultrasound irradiation, singlet oxygen (¹O₂) is generated, which then interacts with tumor-specific ONOO^- to trigger a chemiexcitation process, producing a persistent NIR-II afterglow via chemiluminescence resonance energy transfer (CRET). This synergistic mechanism enables precise spatiotemporal control over afterglow emission, ensuring high tumor selectivity and deep tissue penetration with minimal background interference. Moreover, the enhanced ¹O₂ production facilitates sonodynamic therapy (SDT), effectively abating tumors. This nanoprobe not only improves imaging accuracy but also provides real-time monitoring of therapeutic efficacy, offering a promising approach for personalized cancer treatment and advancement of precision theranostics.