Qing Li,Ning Liu,Dayu Wang,Lie Ma,Mingzhou Wu,Enna Ha,Junqing Hu,Zhe Zhang,Shuqing He
Silver sulfide (Ag 2 S) quantum dots (QDs), which emit light in the near-infrared II window (NIR-II, 1000–1700 nm), exhibit unique and remarkable potential in bioluminescence. However, their widespread application in experimental research is currently limited by a relatively low quantum efficiency. Cation exchange reactions have emerged as a remarkably versatile approach for synthesizing nanomaterials with adjustable structures and customizable compositions. In this study, we developed a NIR-II fluorescent probe based on Sn-doped silver sulfide (Sn-Ag 2 S) QDs via a straightforward cation exchange method. The stoichiometric ratios of precursors play a crucial role in tailoring the optical properties of the resultant materials during structural modifications involving cation exchange processes. By optimizing the ratio of Ag and Sn, we obtained ca. 16-fold quantum yields enhancement of Sn-Ag 2 S QDs in the NIR-II range, specifically around strong emission peak at ca. 1200 nm. Following hydrophilic modification, the Sn-Ag 2 S-GSH/MPA QDs exhibited high NIR-II fluorescence signal signal-to-noise ratio (S/N) with a ca. 1.7-fold increase compared to Ag 2 S-GSH/MPA QDs in the femur of mice, showing significant potential for bone imaging. To further investigate the QDs biodistribution mechanisms within osseous microenvironments, we devised a comprehensive multimodal analytical approach incorporating: (1) optical spectral analysis, (2) ultrastructural validation through transmission electron microscopy (TEM), and (3) spatial resolution mapping via laser scanning confocal microscopy (LSCM). These integrated methodologies consistently demonstrated preferential QDs accumulation within trabecular bone marrow compartments, revealing distinct biodistribution patterns in mineralized tissues.
Skeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Optical imaging through the near-infrared-II window (NIR-II, 1000–1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can passively target the bone marrow, which can be effective for over two months. We therefore develop the high-resolution NIR-II imaging method for bone disease diagnosis, including the 3D bone imaging instrumentation to show the intravital bone morphology. We demonstrate the monitoring of 1 mm bone defects with spatial resolution comparable to the X-ray imaging result. Moreover, NIR-II imaging can reveal the early onset inflammation as the synovitis in the early stage of rheumatoid arthritis, comparable to micro computed tomography (μCT) in diagnosis of osteoarthritis, including the symptoms of osteophyte and hyperostosis in the knee joint.