Controlled Synthesis of Ag2S Quantum Dots and Experimental Determination of the Exciton Bohr Radius

<span lang="EN-US" style="font-family: &quot;Calibri&quot;,&quot;sans-serif&quot;; font-size: 10.5pt; mso-bidi-font-size: 11.0pt; mso-ascii-theme-font: minor-latin; mso-fareast-font-family: 宋体; mso-fareast-theme-font: minor-fareast; mso-hansi-theme-font: minor-latin; mso-bidi-font-family: &quot;Times New Roman&quot;; mso-bidi-theme-font: minor-bidi; mso-ansi-language: EN-US; mso-fareast-language: ZH-CN; mso-bidi-language: AR-SA;"><font color="#000000">Ag2S quantum dots (QDs) have attracted increasing attention due to their appealing optical properties in the near-infrared regime. However, a full understanding of the quantum confinement effect of Ag2S QDs has not been achieved so far. Herein, for the first time, the size-dependent excited state optical properties of Ag2S QDs are systematically investigated by photoluminescence (PL), PL excitation (PLE), and time-resolved PL spectroscopy. Experimentally, we determine the exciton Bohr radius of Ag2S QDs as 2.2 nm, which is highly consistent with theoretical results.</font></span

Real-time in vivo visualization of tumor therapy by a near-infrared-II Ag2S quantum dot-based theranostic nanoplatform

Real-time and objective feedback of therapeutic efficacies would be of great value for tumor treatment. Here, we report a smart Ag2S QD-based theranostic nanoplatform (DOX@PEG-Ag2S) obtained by loading the anti-cancer drug doxorubicin (DOX) into polyethylene glycol-coated silver sulfide quantum dots (PEG-Ag2S QDs) through hydrophobic-hydrophobic interactions, which exhibited high drug loading capability (93 wt.% of DOX to Ag2S QDs), long circulation in blood (t (1/2) = 10.3 h), and high passive tumor-targeting efficiency (8.9% ID/gram) in living mice where % ID/gram reflects the probe concentration in terms of the percentage of the injected dose (ID) per gram of tissue. After targeting the tumor tissue, DOX from PEG-Ag2S cargoes was selectively and rapidly released into cancer cells, giving rise to a significant tumor inhibition. Owing to the deep tissue penetration and high spatio-temporal resolution of Ag2S QDs fluorescence in the second near-infrared window (NIR-II), the DOX@PEG-Ag2S enabled real-time in vivo reading of the drug targeting process and therapeutic efficacy. We expect that such a novel theranostic nanoplatform, DOX@PEG-Ag2S, with integrated drug delivery, therapy and assessment functionalities, will be highly useful for personalized treatments of tumors

Enhanced Nanodrug Delivery to Solid Tumors Based on a Tumor Vasculature-Targeted Strategy

Tumor angiogenesis is a hallmark of tumor growth and metastasis, and inhibition of tumor angiogenesis is an effective strategy for tumor therapy. The high expression levels of specific biomarkers such as integrin receptors (e.g., alpha(v)/beta(3)) in the endothelium of tumor vessels make angiogenesis an ideal target for drug delivery and thus tumor therapy. Herein, a new nanodrug (T&D@RGD-Ag2S) is presented, which can effectively inhibit tumor growth by integrating the specific recognition peptide cyclo(Arg-Gly-Asp-d-Phe-Cys) (cRGD) for tumor vascular targeting, the broad-spectrum endothelial inhibitor O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), and chemotherapeutic drug doxorubicin (DOX) for synergetic tumor therapy. The results show that the T&D@RGD-Ag2S nanodrug rapidly and specifically binds to the tumor vasculature after intravenous injection. Tumor vascular density is greatly reduced following effective angiogenesis inhibition by TNP-470. Meanwhile, increased delivery of DOX deep into the tumor induces extensive tumor apoptosis, resulting in remarkable tumor growth inhibition in a human U87-MG malignant glioma xenograft model. In addition, the therapeutic effects of T&D@RGD-Ag2S on inhibiting tumor growth and decreasing vessel density are monitored in situ using near-infrared II (NIR-II) fluorescence imaging of Ag2S quantum dots. This tumor vasculature-targeted strategy can be extended as a general method for treating a broad range of tumors and holds promise for future clinical applications

In vivo real-time visualization of mesenchymal stem cells tropism for cutaneous regeneration using NIR-II fluorescence imaging

Mesenchymal stem cells (MSCs) have shown great potential for cutaneous wound regeneration in clinical practice. However, the in vivo homing behavior of intravenously transplanted MSCs to the wounds is still poorly understood. In this work, fluorescence imaging with Ag2S quantum dots (QDs) in the second near-infrared (NIR-II) window was performed to visualize the dynamic homing behavior of transplanted human mesenchymal stem cells (hMSCs) to a cutaneous wound in mice. Benefiting from the desirable spatial and temporal resolution of Ag2S QDs-based NIR-II imaging, for the first time, the migration of hMSCs to the wound was dynamically visualized in vivo. By transplanting a blank collagen scaffold in the wound to help the healing, it was found that hMSCs were slowly recruited at the wound after intravenous injection and were predominantly accumulated around the edge of wound. This resulted in poor healing effects in terms of slow wound closure and thin thickness of the regenerated skin. In contrast, for the wound treated by the collagen scaffold loaded with stromal cell derived factor-1 alpha (SDF-1 alpha), more hMSCs were recruited at the wound within a much shorter time and were homogenously distributed across the whole wound area, which enhances the re-epithelialization, the neovascularization, and accelerates the wound healing. (C) 2015 Elsevier Ltd. All rights reserved

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 (similar to 40 mu m) 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.&nbsp

Tracking of Transplanted Human Mesenchymal Stem Cells in Living Mice using Near-Infrared Ag-2 S Quantum Dots

Stem cell therapeutics has emerged as a novel regenerative therapy for tissue repair in the last decade. However, dynamically tracking the transplanted stem cells in vivo remains a grand challenge for stem cell-based regeneration medicine in full understanding the function and the fate of the stem cells. Herein, Ag2S quantum dots (QDs) in the second near-infrared window (NIR-II, 1.0-1.4 m) are employed for dynamically tracking of human mesenchymal stem cells (hMSCs) in vivo with high sensitivity and high spatial and temporal resolution. As few as 1000 Ag2S QDs-labeled hMSCs are detectable in vivo and their fluorescence intensity can maintain up to 30 days. The in situ translocation and dynamic distribution of transplanted hMSCs in the lung and liver can be monitored up to 14 days with a temporal resolution of 100 ms. The in vivo high-resolution imaging indicates the heparin-facilitated translocation of hMSCs from lung to liver as well as the long-term retention of hMSCs in the liver contribute to the treatment of liver failure. The novel NIR-II imaging offers a possibility of tracking stem cells in living animals with both high spatial and temporal resolution, and encourages the future clinical applications in imaging-guided cell therapies

Preoperative Detection and Intraoperative Visualization of Brain Tumors for More Precise Surgery: A New Dual-Modality MRI and NIR Nanoprobe

In clinical practice, it is difficult to identify tumor margins during brain surgery due to its inherent infiltrative character. Herein, a unique dual-modality nanoprobe (Gd-DOTA-Ag2S QDs, referred as Gd-Ag2S nanoprobe) is reported, which integrates advantages of the deep tissue penetration of enhanced magnetic resonance (MR) imaging of Gd and the high signal-to-noise ratio and high spatiotemporal resolution of fluorescence imaging in the second near-infrared window (NIR-II) of Ag2S quantum dots (QDs). Due to the abundant tumor angiogenesis and the enhanced permeability and retention effect in the tumor, a brain tumor (U87MG) in a mouse model is clearly delineated in situ with the help of the Gd assisted T1 MR imaging and the intraoperative resection of the tumor is precisely accomplished under the guidance of NIR-II fluorescence imaging of Ag2S QDs after intravenous injection of Gd-Ag2S nanoprobe. Additionally, no histologic changes are observed in the main organs of the mouse after administration of Gd-Ag2S nanoprobe for 1 month, indicating the high biocompatibility of the nanoprobe. We expect that such a novel Detection and Operation strategy based on Gd-Ag2S nanoprobe is promising in future clinical applications