Expanding NIR-II Lanthanide Toolboxes for Improved Biomedical Imaging and Detection

ConspectusOptical imaging with high spatiotemporal resolution has been developed as a vital technology to reveal biological mysteries. Researchers have made countless profound innovations to promote the investigations on cell biology, especially after the implementation of far-field optical super-resolution imaging technology. Intrinsically, in-depth understanding of physiological activities inevitably requires optical imaging in living organisms at tissue, cell, or even single molecule levels. However, such a requirement usually encounters a great bottleneck because traditional optical imaging has little ability to penetrate biological tissues. Recently, the newly emerged optical imaging technology based on the second near-infrared window (NIR-II, 1000∼1700 nm) has changed this predicament. With suppressed light-scattering and diminished tissue autofluorescence, NIR-II optical imaging can easily achieve micrometer scale resolution at sub-centimeter tissue depth. Therefore, researchers regard it as a new avenue for in vivo optical imaging research.The past decade has witnessed increased interest in the field of in vivo optical imaging in the NIR-II window, accompanied by the significant development of NIR-II luminescence probes including small organic molecules, single-walled carbon nanotubes (SWNTs), quantum dots (QDs), and lanthanide nanoprobes. Among these luminescent probes, lanthanide nanoprobes, including lanthanide nanoparticles and lanthanide complexes, have become one of the most promising contrast agents. Owing to their abundant emissions with a narrow-band, lanthanide nanoprobes are usually favored when performing in vivo multiplexing imaging. In addition, their inherently long luminescence lifetimes (>1 μs) offer them great opportunity to implement time-gated imaging that can efficiently avoid autofluorescence interference. Besides, the superior photostability of lanthanides probes satisfies the requirements of long-term in vivo imaging. Based on these advantages, researchers have carried out extensive exploration on optical properties and functionalities of lanthanide nanoprobes.In this Account, we highlight our contributions to developing the NIR-II lanthanide toolboxes for improved biomedical imaging and detection, with a special focus on the future development of lanthanide nanoprobes for biological applications. First, we summarize our efforts on optimizing the excitation and emission wavelengths of the NIR-II lanthanide nanoprobes and analyze how these wavelengths affect the spatial resolution and penetration depth of in vivo optical imaging. Then, we discuss the time domain relevant achievements that are realized by well-designed lanthanide nanoparticles and luminescence lifetime imaging system. After that, we present the attempts to achieve persistent luminescence lanthanide nanoparticles for excitation-free in vivo optical imaging. We also conclude the breakthroughs in the design and synthesis of lanthanide complexes as well as their unique biological imaging results. At the end, we emphasize the future challenges and developments of the NIR-II lanthanide nanoprobes for in vivo optical imaging. By taking our work as a guide, we hope that this Account will provide the rationale behind the development of the NIR-II lanthanide tools and reveal their future opportunities in bioapplications.