The Near-Infrared-II Fluorophores and Advanced Microscopy Technologies Development and Application in Bioimaging

Ag2Te is one of the most promising semiconductors with a narrow band gap and low toxicity; however, it remains a challenge to tune the emission of Ag2Te quantum dots (QDs) precisely and continuously in a wide range. Herein, Ag2Te QDs emitting from 950 to 2100 nm have been synthesized via trialkylphosphine-controlled growth. Trialkylphosphine has been found to induce the dissolution of small-sized Ag2Te QDs due to its stronger ability to coordinate to the Ag ion than that of 1-octanethiol, predicated by the density functional theory. By controlling this dissolution effect, the monomer supply kinetics can be regulated, achieving precise size control of Ag2Te QDs. This synthetic strategy results in state-of-the-art silver-based QDs with emission tunability. Only by taking advantage of such an ultrawide emission has the sizing curve of Ag2Te been obtained. Moreover, the absolute photoluminescence quantum yield of Ag2Te QDs can reach 12.0% due to their well-passivated Ag-enriched surface with a density of 5.0 ligands/nm2, facilitating noninvasive in vivo fluorescence imaging. The high brightness in the long-wavelength near-infrared (NIR) region makes the cerebral vasculature and the tiny vessel with a width of only 60 μm clearly discriminable. This work reveals a nonclassical growth mechanism of Ag2Te QDs, providing new insight into precisely controlling the size and corresponding photoluminescence properties of semiconductor nanocrystals. The ultrasmall, low-toxicity, emission-tunable, and bright NIR-II Ag2Te QDs synthesized in this work offer a tremendous promise for multicolor and deep-tissue in vivo fluorescence imaging.

Breaking through the Size Control Dilemma of Silver Chalcogenide Quantum Dots via Trialkylphosphine-Induced Ripening: Leading to Ag2Te Emitting from 950 to 2100 nm

Non-toxic and long-term fluorescent probes for tumor imaging are in urgent need for non-invasively obtaining information about tumor genesis and metastasis in vivo. Here, we present a biocompatible near-infrared fluorescent probe for in vivo long-term imaging of tumor by modifying glucose (Glc), which experiences high uptake in cancer cells, on the surface of near-infrared Ag2Se quantum dots (NIR Ag2Se QDs). The fluorescence of glucose-functionalized Ag2Se QDs (Glc-Ag2Se QDs) from the targeted tumor can be observed in vivo for at least 7 days. In addition, this probe could be excreted through kidneys and the renal excretion ability is favorable for in vivo imaging applications. Moreover, Glc-Ag2Se QDs could be used for tumor targeted imaging of not only human breast cancer cells (MCF-7), but also SW1990 pancreatic cancer cells since glucose is highly taken up in almost all kinds of tumors. Glc-Ag2Se QDs could be a promising general tool for in vivo long-term observation of tumor evolution.

Glucose-functionalized near-infrared Ag2Se quantum dots with renal excretion ability for long-term in vivo tumor imaging.

Improving the effectiveness of cancer therapy will require tools that enable more specific cancer targeting and improved tumor visualization. Theranostics have the potential for improving cancer care because of their ability to serve as both diagnostics and therapeutics; however, their diagnostic potential is often limited by tissue-associated light absorption and scattering. Herein, we develop CuInSe2@ZnS:Mn quantum dots (QDs) with intrinsic multifunctionality that both enable the accurate localization of small metastases and act as potent tumor ablation agents. By leveraging the growth kinetics of a ZnS shell on a biocompatible CuInSe2 core, Mn doping, and folic acid functionalization, we produce biocompatible QDs with high near-infrared (NIR)-II fluorescence efficiency up to 31.2%, high contrast on magnetic resonance imaging (MRI), and preferential distribution in 4T1 breast cancer tumors. MRI-enabled contrast of these nanoprobes is sufficient to timely identify small metastases in the lungs, which is critically important for preventing cancer spreading and recurrence. Further, exciting tumor-resident QDs with NIR light produces both fluorescence for tumor visualization through radiative recombination pathways as well as heat and radicals through nonradiative recombination pathways that kill cancer cells and initiate an anticancer immune response, which eliminates tumor and prevents tumor regrowth in 80% of mice.

Xue Zhang

Papers

Ultrasmall Quantum Dots with Broad-Spectrum Metal Doping Ability for Trimodal Molecular Imaging