Kundu Bidyut Kumar, Chen Rui, Diao Jiajie, Sun Yujie
Department of Chemistry, University of Cincinnati, Cincinnati, OH, 45221, USA.
Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
Adv Healthc Mater. 2025 Jan;14(3):e2403272. doi: 10.1002/adhm.202403272. Epub 2024 Nov 21.
Near-infrared (NIR) bioimaging has emerged as a transformative technology in biomedical research. Among many fluorescent probes that are suitable for NIR imaging studies, two-photon absorption (TPA) ones represent a particularly promising category, because TPA fluorescent probes can overcome the inherent limitations of one-photon absorption (OPA) counterparts. By leveraging the unique properties of two-photon absorption, TPA fluorescent probes achieve superior tissue penetration, significantly reduced photodamage, and enhanced spatial resolution. This perspective article delves into the fundamental principles, design strategies, and representative TPA probes for various imaging applications. In particular, a number of molecular fluorescent probes, ranging from organic, inorganic, and COF/MOF-based systems are highlighted to showcase the vast scope of possible TPA probe design and application scenarios. In addition, the employment of stimulated TPA probes that are responsive to different external factors, including pH, redox species, enzymes, and hypoxia, is also discussed. In the end, the future perspectives for the continuous advancement of TPA fluorescent probes in the NIR bioimaging field are presented. For instance, it is essential to transition from cellular to in vivo imaging studies to obtain more physiologically relevant insights. Additionally, the development of "dual-function" TPA probes for both disease diagnosis and therapeutic treatment is particularly promising.
近红外（NIR）生物成像已成为生物医学研究中的一项变革性技术。在众多适用于近红外成像研究的荧光探针中，双光子吸收（TPA）探针是一类特别有前景的探针，因为TPA荧光探针可以克服单光子吸收（OPA）同类探针的固有局限性。通过利用双光子吸收的独特性质，TPA荧光探针实现了卓越的组织穿透性、显著降低的光损伤以及增强的空间分辨率。这篇观点文章深入探讨了各种成像应用的基本原理、设计策略和代表性TPA探针。特别强调了一系列分子荧光探针，包括基于有机、无机以及COF/MOF的体系，以展示TPA探针设计和应用场景的广阔范围。此外，还讨论了对不同外部因素（包括pH值、氧化还原物质、酶和缺氧）有响应的受激TPA探针的应用。最后，介绍了TPA荧光探针在近红外生物成像领域不断发展的未来前景。例如，从细胞成像研究向体内成像研究过渡以获得更多生理相关见解至关重要。此外，开发用于疾病诊断和治疗的“双功能”TPA探针特别有前景。
