Molecularly Locked <i>π</i> ‐Bridge Endows AIEgen with 1064 nm Excitation for Deep Tissue Imaging

Abstract 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.