Symmetry-to-Asymmetry-Engineered Aggregation-Induced Second Near-Infrared Emission Nanoplatform for Nitric Oxide-Enhanced Phototheranostics of Fungal Biofilms.

Fungal biofilm infections pose a serious and growing threat to human health. To address this challenge, we developed a multifunctional nanoplatform (ASE@B NPs) that integrates a second near-infrared (NIR-II) photothermal agent, biofilm-targeting anti-microbial function, and photothermally triggered nitric oxide (NO) release. This system enables precise targeting of the infected microenvironment through a carrier containing acid-responsive segments, thereby achieving combined anti-fungal and anti-inflammatory effects against fungal biofilms. A key to this advance was the enhancement of photothermal conversion efficiency (PCE) via molecular engineering of aggregation-induced emission (AIE)-active NIR-II luminogens. By shifting the donor-acceptor-donor (D-A-D) configuration from symmetric to asymmetric, we successfully converted their emission behavior from aggregation-caused quenching (ACQ) to AIE. Furthermore, by leveraging the acidic biofilm microenvironment and negatively charged surfaces of fungal cells, we employed an amphiphilic polymer carrier incorporating a weak acid-responsive charge-reversal moiety. This carrier was coloaded with a photothermal-responsive NO prodrug (BNN6) and the AIE luminogen. The resulting nanoplatform exhibits a negative surface charge under physiological conditions, ensuring prolonged blood circulation and biosafety, while switching to a positive charge in acidic biofilms to promote penetration and fungal binding. Collectively, this multifunctional nanoplatform enables efficient biofilm disruption and microenvironment reprogramming, offering a promising theranostic strategy for combating drug-resistant fungal infections.