Susumu Kimihiro, Uyeda H Tetsuo, Medintz Igor L, Pons Thomas, Delehanty James B, Mattoussi Hedi
Division of Optical Sciences and Center for Bio/Molecular Science and Engineering, U.S. Naval Research Laboratory, Washington, D.C. 20375, USA.
J Am Chem Soc. 2007 Nov 14;129(45):13987-96. doi: 10.1021/ja0749744. Epub 2007 Oct 23.
We have designed and synthesized a series of modular ligands based on poly(ethylene glycol) (PEG) coupled with functional terminal groups to promote water-solubility and biocompatibility of quantum dots (QDs). Each ligand is comprised of three modules: a PEG single chain to promote hydrophilicity, a dihydrolipoic acid (DHLA) unit connected to one end of the PEG chain for strong anchoring onto the QD surface, and a potential biological functional group (biotin, carboxyl, and amine) at the other end of the PEG. Water-soluble QDs capped with these functional ligands were prepared via cap exchange with the native hydrophobic caps. Homogeneous QD solutions that are stable over extended periods of time and over a broad pH range were prepared. Surface binding assays and cellular internalization and imaging showed that QDs capped with DHLA-PEG-biotin strongly interacted with either NeutrAvidin immobilized on surfaces or streptavidin coupled to proteins which were subsequently taken up by live cells. EDC coupling in aqueous buffer solutions was also demonstrated using resonance energy transfer between DHLA-PEG-COOH-functionalized QDs and an amine-terminated dye. The new functional surface ligands described here provide not only stable and highly water-soluble QDs but also simple and easy access to various biological entities.
我们设计并合成了一系列基于聚乙二醇（PEG）并连接有功能性端基的模块化配体，以提高量子点（QD）的水溶性和生物相容性。每个配体由三个模块组成：一条用于提高亲水性的PEG单链、连接在PEG链一端用于牢固锚定在量子点表面的二氢硫辛酸（DHLA）单元，以及位于PEG另一端的潜在生物功能基团（生物素、羧基和胺基）。通过与天然疏水帽进行帽交换，制备了用这些功能性配体封端的水溶性量子点。制备了在很长一段时间内以及在很宽的pH范围内都稳定的均匀量子点溶液。表面结合试验以及细胞内化和成像表明，用DHLA-PEG-生物素封端的量子点与固定在表面的中性抗生物素蛋白或与蛋白质偶联的链霉亲和素强烈相互作用，随后被活细胞摄取。还利用DHLA-PEG-COOH功能化量子点与胺基末端染料之间的共振能量转移，证明了在水性缓冲溶液中的EDC偶联。这里描述的新型功能性表面配体不仅提供了稳定且高度水溶性的量子点，还提供了简单便捷地接触各种生物实体的途径。
