糖类量子点（glyco-QDs）在生物成像应用中引起了重要的兴趣，特别是在癌症成像中，因为它们有效地将糖团聚效应与量子点的优异光学特性相结合。现在的主要挑战在于如何消除传统有毒Cd基量子点中产生的高重金属毒性，以用于体内生物成像。在这里，我们报告一种环保友好的途径来制备水中无毒Cd-free glyco-QDs，方法是将硫端单糖与金属盐前体进行“直接”反应。糖-CuInS2 QDs的形成可以通过遵循LaMer模型的成核生长机制来解释。预先制备的四种糖-CuInS2 QDs是水溶性的，单分散的，球形的，并表现出3.0-4.0nm的尺寸范围。它们在可见区（500-590nm）和近红外区（~827nm）呈现出良好分离的双发射，这可能归因于可见激子发射和近红外表面缺陷发射。同时，细胞成像显示了在肿瘤细胞（HeLa，A549，MKN-45）中可逆不同的双色（绿色和红色）荧光，并且基于其良好的生物识别能力，糖-CuInS2 QDs具有出色的膜靶向性质。重要的是，这些QDs成功地穿透到三维多细胞肿瘤球体（MCTS）内部（坏死区域）由于它们的高负电荷（zeta电位值范围为-23.9到-30.1mV），克服了现有QDs在体外球体模型中穿透深度不足的问题。因此，共聚焦分析确认了它们穿透和标记肿瘤的出色能力。因此，这些glyco-QDs在体内生物成像中的成功应用证实了这种设计策略是开发廉价和有前途的荧光生物探针的有效、低成本和简单的程序。©2023.作者。

Glyco-quantum dots (glyco-QDs) have attracted significant interest in bioimaging applications, notably in cancer imaging, because they effectively combine the glycocluster effect with the exceptional optical properties of QDs. The key challenge now lies in how to eliminate the high heavy metal toxicity originating from traditional toxic Cd-based QDs for in vivo bioimaging. Herein, we report an eco-friendly pathway to prepare nontoxic Cd-free glyco-QDs in water by the "direct" reaction of thiol-ending monosaccharides with metal salts precursors. The formation of glyco-CuInS2 QDs could be explained by a nucleation-growth mechanism following the LaMer model. As-prepared four glyco-CuInS2 QDs were water-soluble, monodispersed, spherical in shape and exhibited size range of 3.0-4.0 nm. They exhibited well-separated dual emission in the visible region (500-590 nm) and near-infrared range (~ 827 nm), which may be attributable to visible excitonic emission and near-infrared surface defect emission. Meanwhile, the cell imaging displayed the reversibly distinct dual-color (green and red) fluorescence in tumor cells (HeLa, A549, MKN-45) and excellent membrane-targeting properties of glyco-CuInS2 QDs based on their good biorecognition ability. Importantly, these QDs succeed in penetrating uniformly into the interior (the necrotic zone) of 3D multicellular tumor spheroids (MCTS) due to their high negative charge (zeta potential values ranging from - 23.9 to - 30.1 mV), which overcame the problem of poor penetration depth of existing QDs in in vitro spheroid models. So, confocal analysis confirmed their excellent ability to penetrate and label tumors. Thus, the successful application in in vivo bioimaging of these glyco-QDs verified that this design strategy is an effective, low cost and simple procedure for developing green nanoparticles as cheap and promising fluorescent bioprobes.© 2023. The Author(s).