Molecularly Locked π-Bridge Endows AIEgen with 1064 nm Excitation for Deep Tissue Imaging

Developing organic aggregation-induced emission luminogen (AIEgen) excitable with the second near-infrared (NIR-II) light, which offers enhanced tissue penetration and a high maximum permissible exposure to light, is highly advantageous for bioimaging applications but remains a significant challenge. In this work, the molecular lock strategy is employed to fuse two alkyl-substituted thiophenes, leading to the design of alkyl-substituted dithieno[3,2-b:2′,3′-d]pyrrole (aDTP). This novel π-bridge features a planar structure with strong electron-donating capability while suppressing intermolecular π–π interactions, enabling the construction of an NIR-II absorption-active AIEgen, named aDTP-TPA. The enhanced π-conjugation and donor-acceptor interactions of aDTP-TPA result in NIR-II absorption and an increased molar extinction coefficient (ɛ), exhibiting superior photophysical properties compared to its thiophene-based counterparts, C6T-TPA and DC6T-TPA. When formulated into water-soluble nanoparticles (NPs), aDTP-TPA NPs demonstrate remarkable tissue penetration depth and improved imaging resolution. In vivo studies, systemic blood vessel angiography, mesenteric circulation imaging, brain vasculature visualization, and NIR-II-guided tumor surgery underscore the exceptional imaging capabilities of these NPs for biomedical applications. This work highlights that the molecularly locked π-bridge strategy holds great promise for developing AIEgens with NIR-II excitation, paving the way for advanced NIR-II bioimaging applications.