Guangcun Chen

Ag2S Quantum Dot: A Bright and Biocompatible Fluorescent Nanoprobe in the Second Near-Infrared Window

Ag(2)S quantum dots (QDs) emitting in the second near-infrared region (NIR-II, 1.0-1.4 μm) are demonstrated as a promising fluorescent probe with both bright photoluminescence and high biocompatibility for the first time. Highly selective in vitro targeting and imaging of different cell lines are achieved using biocompatible NIR-II Ag(2)S QDs with different targeting ligands. The cytotoxicity study illustrates the Ag(2)S QDs with negligible effects in altering cell proliferation, triggering apoptosis and necrosis, generating reactive oxygen species, and causing DNA damage. Our results have opened up the possibilities of using these biocompatible Ag(2)S QDs for in vivo anatomical imaging and early stage tumor diagnosis with deep tissue penetration, high sensitivity, and elevated spatial and temporal resolution owing to their high emission efficiency in the unique NIR-II imaging window.

In vivo real-time visualization of tissue blood flow and angiogenesis using Ag2S quantum dots in the NIR-II window

Improving the tissue penetration depth and spatial resolution of fluorescence-based optical nanoprobes remains a grand challenge for their practical applications in in vivo imaging, due to the scattering and absorption and endogenous autofluorescence of living tissues. Here, we present that Ag2S quantum dots (QDs), containing no toxic ions, exhibiting long circulation time and high stability, act as a new kind of fluorescent probes in the second near-infrared window (NIR-II, 1000-1350 nm) which enable in vivo monitoring of lymphatic drainage and vascular networks with deep tissue penetration and high spatial and temporal resolution. In addition, NIR-II fluorescence imaging with Ag2S QDs provide ultrahigh spatial resolution (~40 μm) that permits us to track angiogenesis mediated by a tiny tumor (2-3 mm in diameter) in vivo. Our results indicate that Ag2S QDs are promising NIR-II fluorescent nanoprobes that could be useful in surgical treatments such as sentinel lymph node (SLN) dissection as well in assessment of blood supply in tissues and organs and screening of anti-angiogenic drugs.

Fates of Fe3O4 and Fe3O4@SiO2 nanoparticles in human mesenchymal stem cells assessed by synchrotron radiation-based techniques

Superparamagnetic iron oxide nanoparticles (SPIOs) have been widely used as the magnetic resonance imaging (MRI) contrast agent in biomedical studies and clinical applications, with special interest recently in in vivo stem cell tracking. However, a full understanding of the fate of SPIOs in cells has not been achieved yet, which is particularly important for stem cells since any change of the microenvironment may disturb their propagation and differentiation behaviors. Herein, synchrotron radiation-based X-ray fluorescence (XRF) in combination with X-ray absorption spectroscopy (XAS) were used to in situ reveal the fate of Fe3O4 and Fe3O4@SiO2 NPs in human mesenchymal stem cells (hMSCs), in which the dynamic changes of their distribution and chemical speciation were precisely determined. The XAS analysis evidences that Fe3O4 NPs cultured with hMSCs are quite stable and almost keep their initial chemical form up to 14 days, which is contradictory to the previous report that Fe3O4 NPs were unstable in cell labeling assessed by using a simplified lysosomal model system. Coating with a SiO2 shell, Fe3O4@SiO2 NPs present higher stability in hMSCs without detectable changes of their chemical form. In addition, XRF analysis demonstrates that Fe3O4@SiO2 NPs can label hMSCs in a high efficiency manner and are solely distributed in cytoplasm during cell proliferation, making it an ideal probe for in vivo stem cell tracking. These findings with the help of synchrotron radiation-based XAS and XRF improve our understanding of the fate of SPIOs administered to hMSCs and will help the future design of SPIOs for safe and efficient stem cells tracking.

Engineered Multifunctional Nanomedicine for Simultaneous Stereotactic Chemotherapy and Inhibited Osteolysis in an Orthotopic Model of Bone Metastasis

A novel multifunctional Ag2 S quantum dot (QD)-based nanomedicine of alendronate (Ald)/doxorubicin (DOX)@Ag2 S is developed for highly effective bone tumor therapy in an orthotopic model. The bone-targeting and osteolysis inhibition of Ald and the chemotherapeutic effect of DOX on the bone tumor are in situ visualized by Ag2 S QDs with emission in the second near-infrared window.

Revealing the Fate of Transplanted Stem Cells In Vivo with a Novel Optical Imaging Strategy

Stem-cell-based regenerative medicine holds great promise in clinical practices. However, the fate of stem cells after transplantation, including the distribution, viability, and the cell clearance, is not fully understood, which is critical to understand the process and the underlying mechanism of regeneration for better therapeutic effects. Herein, we develop a dual-labeling strategy to in situ visualize the fate of transplanted stem cells in vivo by combining the exogenous near-infrared fluorescence imaging in the second window (NIR-II) and endogenous red bioluminescence imaging (BLI). The NIR-II fluorescence of Ag2 S quantum dots is employed to dynamically monitor the trafficking and distribution of all transplanted stem cells in vivo due to its deep tissue penetration and high spatiotemporal resolution, while BLI of red-emitting firefly luciferase (RfLuc) identifies the living stem cells after transplantation in vivo because only the living stem cells express RfLuc. This facile strategy allows for in situ visualization of the dynamic trafficking of stem cells in vivo and the quantitative evaluation of cell translocation and viability with high temporal and spatial resolution, and thus reports the fate of transplanted stem cells and how the living stem cells help, regeneration, for an instance, of a mouse with acute liver failure.

Recent Advances in Tracking the Transplanted Stem Cells Using Near-Infrared Fluorescent Nanoprobes: Turning from the First to the Second Near-Infrared Window

Stem cell-based regenerative medicine has attracted tremendous attention for its great potential to treat numerous incurable diseases. Tracking and understanding the fate and regenerative capabilities of transplanted stem cells is vital for improving the safety and therapeutic efficacy of stem cell-based therapy, therefore accelerating the clinical application of stem cells. Fluorescent nanoparticles (NPs) have been widely used for in vivo tracking of the transplanted stem cells. Among these fluorescent NPs, near-infrared (NIR) NPs have greatly improved the sensitivity, tissue penetration depth, spatial and temporal resolutions of the fluorescence imaging-based stem cell tracking technologies due to the reduced absorption, scattering, and autofluorescence of NIR fluorescence in tissues. Here, this review summarizes the recent studies regarding the tracking of transplanted stem cells using NIR NPs and emphasizes the recent advances of fluorescence imaging in the second NIR window (NIR-II, 1000-1700 nm). Furthermore, the challenges and future prospects of the NIR NP-based technologies are also discussed.

Programmable Chemotherapy and Immunotherapy against Breast Cancer Guided by Multiplexed Fluorescence Imaging in the Second Near‐Infrared Window

Combined chemotherapy and immunotherapy have demonstrated great potential in cancer treatment. However, it is difficult to provide clear information of the pharmacokinetics and pharmacodynamics of chemodrugs and transplanted immune cells in vivo by traditional approaches, resulting in inadequate therapy. Here, a multiplexed intravital imaging strategy by using fluorescence in the second near-infrared window (NIR-II) is first developed to visualize the two events of chemotherapy and immunotherapy in vivo, so that a combinational administration is programed to improve the therapeutical effects against a mouse model of human breast cancer. In detail, Ag2 Se quantum dots (QDs) (λEm = 1350 nm) loaded with stromal-cell-derived factor-1α (SDF-1α) and chemodrug doxorubicin (DOX) are first administrated to deliver the SDF-1α and DOX to the tumor site. After their arrival, monitored by Ag2 Se QD fluorescence, natural killer (NK)-92 cells labeled with Ag2 S QDs (λEm = 1050 nm) are intravenously injected so that the cells are recruited to the tumor by the chemotaxis of SDF-1α, which is visualized by Ag2 S QD fluorescence. Such an imaging approach allows simultaneous evaluation of the behaviors of individual injections in vivo, and facilitates optimized administration regimens, resulting in enhanced tumor inhibition.