Rabies Virus Targeting NIR-II Phototheranostics

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 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 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 to bind to the RVG, allowing for real-time NIR-II fluorescence imaging. Addi-tionally, 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.