Organic NIR‐II Nanofluorophore with Ultrahigh Quantum Yield for Vessels Imaging and Fluorescence Image‐Guided Surgery

Abstract The second near‐infrared window (NIR‐II) fluorescence imaging has aroused more and more interest in biomedical applications due to negligible autofluorescence and deep penetration ability. However, the fluorescence quantum yield of NIR‐II fluorophores with more than 1100 nm emission wavelength is typically less than 1%, thus limiting the imaging quality of deep tissues. In this study, a novel NIR‐II organic small molecule CTB1125 is designed and synthesized. Due to an efficient intramolecular charge transfer (ICT) facilitated by a high donor‐acceptor‐donor (D‐A‐D) strength structure, CTB1125 exhibits a maximum emission wavelength of 1125 nm. Additionally, branched alkyl chains are modified on the conjugated fused ring backbone to reduce intermolecular stacking. CTB1125 is encapsulated in the amphiphilic copolymer PS 2000 ‐PEG 2000 to form CTB1125‐NPs, which exhibit ultrahigh fluorescence quantum yield up to 4.84% in aqueous solution, excellent photostability, and high signal‐to‐noise rate. Due to these outstanding properties, CTB1125‐NPs have been successfully used for clear and long‐duration NIR‐II vessel imaging with small amounts of CTB1125‐NPs, low laser power and short exposure time, and precisely guiding the surgical resection of tumors in mice through fluorescence imaging. This work provides a promising NIR‐II fluorophore with ultrahigh brightness for deep‐tissue imaging and imaging‐guided surgery.