Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
Biomacromolecules. 2012 Sep 10;13(9):2704-15. doi: 10.1021/bm300653v. Epub 2012 Aug 10.
Synthesizing nanocarriers with stealth properties and delivering a "payload" to the particular organ remains a big challenge but is the prime prerequisite for any in vivo application. As a nontoxic alternative to the modification by poly(ethylene glycol) PEG, we describe the synthesis of cross-linked hydroxyethyl starch (HES, M(w) 200,000 g/mol) nanocapsules with a size range of 170-300 nm, which do not show nonspecific uptake into cells. The specific uptake was shown by coupling a folic acid conjugate as a model targeting agent onto the surface of the nanocapsules, because folic acid has a high affinity to a variety of human carcinoma cell lines which overexpress the folate receptor on the cell surface. The covalent binding of the folic acid conjugate onto HES capsules was confirmed by FTIR and NMR spectroscopy. The coupling efficiency was determined using fluorescence spectroscopy. The specific cellular uptake of the HES nanocapsules after folic acid coupling into the folate-receptor presenting cells was studied by confocal laser scanning microscopy (CLSM) and flow cytometry.
合成具有隐身特性的纳米载体，并将“有效载荷”递送到特定器官仍然是一个巨大的挑战，但这是任何体内应用的首要前提。作为对聚乙二醇（PEG）修饰的无毒替代物，我们描述了具有 170-300nm 尺寸范围的交联羟乙基淀粉（HES，Mw 200,000g/mol）纳米胶囊的合成，其不会显示非特异性进入细胞。通过将叶酸缀合物作为模型靶向剂偶联到纳米胶囊的表面上，显示出了特异性摄取，因为叶酸与多种人类癌细胞系具有高亲和力，这些细胞系在细胞表面过度表达叶酸受体。通过傅里叶变换红外（FTIR）和核磁共振（NMR）光谱证实了叶酸缀合物与 HES 胶囊的共价结合。使用荧光光谱法测定偶联效率。通过共聚焦激光扫描显微镜（CLSM）和流式细胞术研究了叶酸偶联后进入叶酸受体表达细胞的 HES 纳米胶囊的特异性细胞摄取。
