Naylor-Adamson Leigh, Price Thomas W, Booth Zoe, Leonard Sophie V L, Gallo Juan, Tung Le Duc, Harvell-Smith Stanley, Thi Kim Thanh Nguyen, Aslam Zabeada, Allsup David, Hondow Nicole, Chamberlain Thomas, Schneider Jürgen E, Naseem Khalid, Bouillard Jean-Sebastien G, Stasiuk Graeme J, Calaminus Simon D J
Biomedical Institute for Multimorbidity, Hull York Medical School, University of Hull, Hull, HU6 7RX, UK.
Department of Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, King's College London, London, SE1 7EH, UK.
J Mater Chem B. 2025 Jan 15;13(3):1052-1063. doi: 10.1039/d4tb01334d.
Quantum dots (QDs) are semiconducting inorganic nanocrystals, that have garnered interest in biological and medical spheres due, to their potential benefits in biomedical imaging and drug-delivery systems. Indium phosphide QDs shelled with zinc sulphide (InP/ZnS) are viewed as more biocompatible than previous heavy metal based QDs. However, little is known about how InP/ZnS QDs affect a key blood cell, the platelet. Understanding how platelets interact with QDs is critical as unwanted activation can lead to pathological thrombus formation. Herein, we demonstrate PEGylation of InP/ZnS QDs coated with lipoic acid (QD-LA) or coated with penicillamine (QD-Pen) surface ligands induced markedly less platelet aggregation, platelet-QD interactions, integrin activation, alpha granule secretion and restored platelet spreading in washed platelets in comparison to their non-PEGylated counterparts. Furthermore, in whole blood, PEGylation of QDs reduced the number of QDs in the thrombus, thereby helping to minimise the chance of dysfunctional thrombus formation. Overall, we show that QD PEGylation is important to help prevent QD mediated platelet activation. In combination with the most biocompatible coating, PEGylation markedly reduced platelet activation, widening the concentrations at which QDs were viable for development as potential drug delivery or imaging agents.
量子点(QDs)是半导体无机纳米晶体,因其在生物医学成像和药物递送系统中的潜在优势而在生物和医学领域引起了关注。包覆硫化锌的磷化铟量子点(InP/ZnS)被认为比以前基于重金属的量子点具有更高的生物相容性。然而,关于InP/ZnS量子点如何影响关键血细胞——血小板,人们知之甚少。了解血小板如何与量子点相互作用至关重要,因为不必要的激活会导致病理性血栓形成。在此,我们证明,与未聚乙二醇化的对应物相比,用硫辛酸(QD-LA)或青霉胺(QD-Pen)表面配体包覆的InP/ZnS量子点的聚乙二醇化在洗涤后的血小板中诱导的血小板聚集、血小板-量子点相互作用、整合素激活、α颗粒分泌明显减少,并恢复了血小板铺展。此外,在全血中,量子点的聚乙二醇化减少了血栓中量子点的数量,从而有助于将功能失调性血栓形成的几率降至最低。总体而言,我们表明量子点聚乙二醇化对于帮助防止量子点介导的血小板激活很重要。与最具生物相容性的涂层相结合,聚乙二醇化显著降低了血小板激活,拓宽了量子点作为潜在药物递送或成像剂可行的浓度范围。