Department of Physical and Analytical Chemistry, University of Oviedo , Avda. Julian Claveria 8, E-33006 Oviedo, Spain.
Life Sciences Department, International Iberian Nanotechnology Laboratory (INL) , Av. Mestre José Veiga, 4715-330 Braga, Portugal.
Langmuir. 2017 Jun 27;33(25):6333-6341. doi: 10.1021/acs.langmuir.7b00409. Epub 2017 Jun 12.
Colloidal Mn-doped ZnS quantum dots (QDs) were synthesized, surface modified, and thoroughly characterized using a pool of complementary techniques. Cap exchange of the native l-cysteine coating of the QDs with dihydrolipoic acid (DHLA) ligands is proposed as a strategy to produce nanocrystals with a strong phosphorescent-type emission and improved aqueous stability. Moreover, such a stable DHLA coating can facilitate further bioconjugation of these QDs to biomolecules using established reagents such as cross-linker molecules. First, a structural and morphological characterization of the l-cysteine QD core was performed by resorting to complementary techniques, including X-ray powder diffraction (XRD) and microscopy tools. XRD patterns provided information about the local structure of ions within the nanocrystal structure and the number of metal atoms constituting the core of a QD. The judicious combination of the data obtained from these complementary characterization tools with the analysis of the QDs using inductively coupled plasma-mass spectrometry (ICP-MS) allowed us to assess the number concentration of nanoparticles in an aqueous sample, a key parameter when such materials are going to be used in bioanalytical or toxicological studies. Asymmetric flow field-flow fractionation (AF4) coupled online to ICP-MS detection proved to be an invaluable tool to compute the number of DHLA molecules attached to the surface of a single QD, a key feature that is difficult to estimate in nanoparticles and that critically affects the behavior of nanoparticles when entering the biological media (e.g., cellular uptake, biodistribution, or protein corona formation). This hybrid technique also allowed us to demonstrate that the elemental composition of the nanoparticle core remains unaffected after the ligand exchange process. Finally, the photostability and robustness of the DHLA-capped QDs, critical parameters for bioanalytical applications, were assessed by molecular luminescence spectroscopy.
胶态 Mn 掺杂的 ZnS 量子点 (QD) 被合成、表面修饰，并使用一系列互补技术进行了全面表征。我们提出了用二氢硫辛酸 (DHLA) 配体交换 QD 中原有的 l-半胱氨酸涂层的策略，以产生具有强磷光型发射和提高水稳定性的纳米晶体。此外，这种稳定的 DHLA 涂层可以促进这些 QD 与生物分子的进一步生物偶联，使用交联剂等现有试剂。首先，通过使用互补技术，包括 X 射线粉末衍射 (XRD) 和显微镜工具，对 l-半胱氨酸 QD 核的结构和形态进行了表征。XRD 图谱提供了关于纳米晶体结构中离子局部结构和构成 QD 核的金属原子数量的信息。将这些互补表征工具获得的数据与使用电感耦合等离子体质谱 (ICP-MS) 对 QD 进行的分析相结合，使我们能够评估水溶液中纳米颗粒的数浓度，这是在生物分析或毒理学研究中使用此类材料时的关键参数。不对称流场流分离 (AF4) 与 ICP-MS 检测在线联用被证明是一种非常有价值的工具，可以计算单个 QD 表面附着的 DHLA 分子的数量，这是一个难以估计的关键特性纳米颗粒，当纳米颗粒进入生物介质时，这会严重影响纳米颗粒的行为（例如，细胞摄取、生物分布或蛋白质冠形成）。这种混合技术还使我们能够证明配体交换过程后纳米颗粒核的元素组成保持不变。最后，通过分子发光光谱评估了 DHLA 封端的 QD 的光稳定性和鲁棒性，这是生物分析应用的关键参数。
