- The full article entitled “Achieving High-Brightness NIR-II Emission: Molecular Locking and Wrapping Strategies in Fluorescent Material Design for in Vivo Bioimaging” can now be found at the Advanced Materials website at https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202510386
- Authors: Yingpeng Wan, Yijian Gao, Yu-Neng Chen, Ka-Wai Lee, Hao-Wen Wang, Ya-Jie Tsai, Weilong Chen, Shengliang Li,* Ken-Tsung Wong,* and Chun-Sing Lee*
The near-infrared-II window (NIR-II, 900–1700 nm) offers great potential in biomedical diagnostics and image-guided therapy due to its advantages of deep tissue penetration and low background autofluorescence. However, the development of small-molecule NIR-II fluorophores has faced longstanding challenges. Structural torsion in organic π-conjugated molecules can reduce absorption strength, while aggregation-caused quenching (ACQ) occurring in nanoparticle formulations further diminishes emission brightness. Thus, designing dyes with both strong absorption and bright NIR-II fluorescence remains highly demanding.
A recent publication from Prof. Ken-Tsung Wong’s group in Advanced Materials demonstrates a dual-strategy breakthrough based on “structural locking” and “side-chain wrapping.” In this work, the team first applied a molecular-locking modification on the original DTTD fluorophore, reinforcing the π-bridge that otherwise undergoes rotational distortion and leads to a lower extinction coefficient. This resulted in the derivative DMTTD (see figure below), achieving a significantly enhanced extinction coefficient of 3.57 × 10⁴ M⁻¹ cm⁻¹ and effectively improving light absorption.
To further mitigate ACQ within nanoparticles—caused by overly close intermolecular packing—the researchers introduced a side-chain wrapping strategy by replacing methyl groups with bulky branched alkyl chains. This modification generated the dye DETTD, which exhibited a substantial enhancement in emission brightness, increasing from 22.6 M⁻¹ cm⁻¹ for DTTD to 117.5 M⁻¹ cm⁻¹ for DETTD—an improvement of more than five-fold.
In vivo studies conducted in collaboration with research teams at City University of Hong Kong and Soochow University demonstrated that these NIR-II fluorophores can clearly visualize mouse vasculature and gastrointestinal structures with high contrast. Altogether, this research establishes two effective strategies to increase fluorophore absorption while suppressing aggregation-induced quenching, providing valuable design guidelines for the development of next-generation high-brightness NIR-II fluorescent materials.
