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

Abstract 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.