Pyrrolopyrrole aza-BODIPY-based NIR-II fluorophores for in vivo dynamic vascular dysfunction visualization of vascular-targeted photodynamic therapy.

Abstract

Real-time monitoring vascular responses is crucial for evaluating the therapeutic effects of vascular-targeted photodynamic therapy (V-PDT). Herein, we developed a highly-stable and bright aggregation induced emission (AIE) fluorophore (PTPE3 NP) for dynamic fluorescence (FL) imaging of vascular dysfunction beyond 1300 nm window during V-PDT. The superior brightness (ϵ_maxΦ_{f>1000 nm} ≈ 180.05 M^-1 cm^-1) and high resolution of PTPE3 NP affords not only high-clarity images of whole-body and local vasculature (hindlimbs, mesentery, and tumor) but also high-speed video imaging for tracking blood circulation process. By virtue of the NPs' prolonged blood circulation time (t_1/2 ≈ 86.5 min) and excellent photo/chemical (pH, RONS) stability, mesenteric and tumor vascular dysfunction (thrombosis formation, vessel occlusion, and hemorrhage) can be successfully visualized during V-PDT by FL imaging for the first time. Furthermore, the reduction of blood flow velocity (BFV) can be monitored in real time for precisely evaluating efficacy of V-PDT. These provide a powerful approach for assessing vascular responses during V-PDT and promote the development of advanced fluorophores for biological imaging.