Bacterial infections significantly alter the local microenvironment, with acidic byproducts from bacterial metabolism leading to a pronounced pH reduction. Leveraging this characteristic, we synthesized and identified DHTPA, a near‐infrared (NIR) fluorescent and pH‐responsive aggregation‐induced emission (AIE) photosensitizer, for enhanced photodynamic therapy against bacterial infections. DHTPA aggregates exhibit a 2.1‐fold increase in ROS generation under weakly acidic conditions (pH 5.5) compared to neutral conditions (pH 7.4), attributed to its pH‐dependent electronic structure modulation. Upon NIR light irradiation, DHTPA aggregates precisely respond to the acidic microenvironment, significantly boosting ROS production for efficient bacterial eradication. In vitro studies demonstrated that DHTPA achieved over 99.9% bactericidal efficiency against both gram‐negative and gram‐positive bacteria. In a murine infected wound model, DHTPA treatment accelerated wound healing by 2.4 times, markedly reduced bacterial burden, and alleviated inflammatory responses, highlighting its therapeutic potential. By integrating NIR activation, pH responsiveness, and AIE properties, DHTPA presents a precise and efficient antibacterial therapeutic strategy, offering an innovative solution for the clinical management of bacterial infections.

Rabies is a viral disease with an almost 100% fatality rate, primarily transmitted through bites from infected animals, with a long incubation period and no effective clinical treatments to date. Herein, we developed the first fluorescent nanotheranostic probe in the second near-infrared (NIR) window capable of efficiently crossing the blood-brain barrier (BBB), precisely targeting rabies virus (RABV), and enabling safe photodynamic therapy (PDT). This probe is based on a novel NIR-II organic polyacetylene fluorophore, DK, which self-assembles via a click reaction with a nanoparticle carrier, N3-PEG2000-R, that we synthesized with a high biocompatibility and BBB permeability. The probe surface is further modified with an aptamer that specifically binds to RABV glycoprotein (RVG), resulting in our final nanotheranostic probe, DK@RA-PEG. Upon intravenous injection into mice, it effectively crosses the BBB, localizes to the infection site, and binds to the RVG, allowing for real-time NIR-II fluorescence imaging. Additionally, it efficiently converts light energy into chemical energy without generating thermal effects, ensuring safe and effective PDT. This advanced nanotheranostic probe integrates precise targeting, deep-tissue imaging, and safe therapy, making it a promising candidate for future clinical applications in rabies treatment.

Breast cancer has now overtaken lung cancer as the “world’s leading cancer,” yet detecting and implementing effective therapies remains a significant challenge. Substantial advances have been made in photothermal therapy (PTT), where photosensitizers use photonic energy to induce localized hyperthermia for cancer eradication. This pioneering approach is gaining traction in clinical settings. However, traditional PTT faces inherent limitations, including the risk of damage to neighboring healthy tissues and potential inflammatory responses due to overheating. Drawing inspiration from the distinct characteristics of aggregation-induced emission the small molecule, PM331, was chosen for study. This donor–acceptor–donor system displays good photothermal conversion efficiencies (40% and 66%) upon excitation at 808 nm and 1,064 nm, respectively. It is also characterized by attractive optical features in the second near-infrared (NIR-II) window. Using nanoparticles containing PM331, PM331@F127 , we have developed a PTT strategy, termed dual-laser PTT (DLPTT), that involves successive excitation using 808 nm and 1,064 nm lasers guided by both NIR-II fluorescence and photoacoustic imaging. The DLPTT strategy involves two steps. First, it initiates DNA damage and downregulates heat shock protein expression as the result of an initial brief irradiation with an 808 nm laser. This is then followed by irradiation with a 1,064 nm laser to ablate tumor cells while minimizing inflammation and harm to surrounding healthy tissues. Based on the findings reported here, we suggest that DLPTT could represent an attractive approach to precision medicine and one that could make PTT more amenable to clinical implementation.