NIR‐II Fluorescent Nanotheranostics with a Switchable Irradiation Mode for Immunogenic Sonodynamic Therapy

Nanotheranostics, which integrate diagnostic and therapeutic functionalities, offer significant potential for tumor treatment. However, current nanotheranostic systems typically involve multiple molecules, each providing a singular diagnostic or therapeutic function, leading to challenges such as complex structural composition, poor targeting efficiency, lack of spatiotemporal control, and dependence on a single therapeutic modality. This study introduces NP^RBOXA, a nanoparticle functionalized with surface-bound cRGD for targeted delivery to α_vβ₃/α_vβ₅ receptors on tumor cells, achieving theranostic integration by sequentially switching its irradiation modes. Under 808 nm laser irradiation, NP^RBOXA emits NIR-II fluorescence, which aids in identifying the nanoparticle's location and fluorescence intensity, thereby determining the optimal treatment window. Following this, the irradiation mode switches to ultrasound irradiation at the optimal treatment window. Ultrasound irradiation induces NP^RBOXA to generate reactive oxygen species, promoting the reduction of OXA-IV to OXA-II, which in turn triggers immunogenic cell death. This mechanism enables a combination of sonodynamic therapy, chemotherapy, and immunotherapy for tumor treatment. The versatile design of NP^RBOXA holds promise for advancing precision oncology through enhanced therapeutic efficacy and real-time imaging guidance.