Bilateral Synergistic Effects of Phototherapy-Based NIR-II Absorption Photosensitizer for Allergic Rhinitis.

Allergic rhinitis (AR) is the most prevalent global health issue, affecting approximately 3 billion people, with its incidence increasing annually. The current first-line pharmacotherapy for symptom relief has limited efficacy and often results in notable side effects. Here, aza-BODIPY-based nanoparticles (RH@NPs) are developed that exhibit mild photothermal therapy (PTT) and type I photodynamic therapy (PDT) capabilities. Enhanced intramolecular charge transfer induces NIR-II absorption of the photosensitizer (RH), facilitating deeper tissue penetration for augmented AR therapy. Additionally, the use of an asymmetric donor-acceptor-acceptor' configuration promotes the self-assembly of RH, enhancing its intersystem crossing ability and enabling efficient photophysical activity. The synergistic effects of PTT (enhancing HSF1 DNA-binding activity to inhibit epithelial-mesenchymal transition by epigenetically regulating the expression of epithelial-mesenchymal transition-associated genes) and PDT (activating NRF2 transcriptional activity to stimulate the antioxidant defense system) enable RH@NPs to provide a superior therapeutic effect in a mouse model of AR. This effect is achieved by mechanically reducing the allergic response rather than merely alleviating symptoms. Notably, the photosensitizer-based physical therapy demonstrates enhanced safety. This study is the first to successfully investigate the application of phototherapy for AR and elucidate its mechanism of action, offering a novel, straightforward, and efficient treatment strategy for AR.