A Quenching‐Resistant Donor–Acceptor–Donor Fluorophore Encapsulated in Erythrocyte Membrane for Efficient Near‐Infrared‐II Fluorescence Imaging

Molecular near‐infrared‐II (NIR‐II) dyes are promising candidates for biological imaging applications; however, numerous NIR‐II fluorophores frequently have issues with suboptimal quantum yield (QY) and unwanted liver accumulation. Here, we developed a novel organic NIR‐II fluorophore (TQBF) with antifluorescence quenching properties through ingenious electron acceptor‐side steric engineering. This rational design prevents undesired π –π interactions while maintaining the planarity of the conjugated molecular core, thereby conferring excellent NIR‐II fluorescence brightness, with a QY as high as 7.2%. To enhance its biomedical utility, TQBF was encapsulated using erythrocyte membranes as the carrier (named TQBF@EM), which demonstrated an efficient NIR‐II fluorescent contrast agent for high‐resolution imaging of microvessels, lymph nodes, and tumors throughout the entire body, while offering excellent biocompatibility and low liver retention. These findings demonstrate that functionalization on the acceptor unit represents a highly valuable strategy for constructing brightness NIR‐II donor–acceptor–donor fluorophores.