NIR-activatable aza-BODIPY nanoparticles for photoacoustic imaging and synergistic NO-photothermal cancer therapy.

Near-infrared (NIR) photothermal therapy (PTT) has emerged as a promising modality for cancer treatment due to its minimal invasiveness, precise spatiotemporal control, and potent therapeutic outcomes. However, the clinical application of photothermal agents (PTAs) remains limited by issues such as poor biodegradability, long-term toxicity, and insufficient photothermal conversion efficiency. Herein, we report the development of a novel amphiphilic aza-boron-dipyrromethene (aza-BODIPY)-based photothermal agent, C8-NBDP-OEG4, which self-assembles into monodisperse nanoparticles in aqueous solution. These nanoparticles exhibit excellent chemical and photostability, along with a high photothermal conversion efficiency of 39.8% under 808 nm laser irradiation. To endow the system with multifunctionality, the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) was co-encapsulated within the nanoparticles, enabling NIR-triggered NO release. This design achieves a dual-mode therapeutic strategy, combining localized hyperthermia and NO-mediated modulation of the tumor microenvironment, thereby significantly enhancing anticancer efficacy. Importantly, the released NO was found to amplify the photoacoustic (PA) signal intensity, facilitating photoacoustic imaging-guided therapy. Both in vitro and in vivo studies demonstrated pronounced tumor growth inhibition with minimal systemic toxicity. Collectively, our study introduces C8-NBDP-OEG4@NO nanoparticles as a multifunctional theranostic nanoplatform, offering NIR-activated, PA imaging-guided synergistic NO-photothermal therapy and showcasing strong potential for precise and effective cancer treatment.