Bassi B, Dacarro G, Galinetto P, Giulotto E, Marchesi N, Pallavicini P, Pascale A, Perversi S, Taglietti A
Dipartimento di Chimica, Sezione di Chimica Generale, Università di Pavia, viale Taramelli, 12-27100 Pavia, Italy.
Nanotechnology. 2018 Jun 8;29(23):235301. doi: 10.1088/1361-6528/aab74f. Epub 2018 Mar 16.
The last decade has come across an increasing demand for theranostic biocompatible nanodevices possessing the double ability of diagnosis and therapy. In this work, we report the design, synthesis and step-by-step characterization of rationally coated gold nanostars (GNSs) for the SERS imaging and photothermal therapy of HeLa cancer cells. The nanodevices were realized by synthesizing GNSs with a seed growth approach, coating them with a controlled mixture of thiols composed of a Raman reporter and a polyethylene glycol with a terminal amino group, and then reacting these amino groups with folic acid (FA), in order to impart selectivity towards cancer cells which overexpress folate receptors on their membranes. After a complete characterization, we demonstrate that these FA-functionalized GNSs (FA-GNSs) are able to bind selectively to the membranes of HeLa cells, acting as SERS tags and allowing SERS imaging. Moreover, we demonstrate that once bound to HeLa cell membranes, FA-GNSs exhibit photothermal effect which can be exploited to kill the same cells in vitro using laser irradiation in the NIR at a very low and safe irradiance. We thus demonstrate that the FA-GNSs designed following the described approach are an efficient prototype of theranostic nanodevices.
在过去十年中,对具有诊断和治疗双重能力的治疗诊断型生物相容性纳米器件的需求日益增加。在这项工作中,我们报告了用于HeLa癌细胞的表面增强拉曼光谱(SERS)成像和光热治疗的合理包覆金纳米星(GNSs)的设计、合成及逐步表征。通过种子生长法合成GNSs,用由拉曼报告分子和带有末端氨基的聚乙二醇组成的硫醇的可控混合物包覆它们,然后使这些氨基与叶酸(FA)反应,从而实现对在其膜上过度表达叶酸受体的癌细胞的选择性识别,进而制备出这种纳米器件。经过全面表征后,我们证明这些叶酸功能化的GNSs(FA-GNSs)能够选择性地结合到HeLa细胞的膜上,充当SERS标签并实现SERS成像。此外,我们证明一旦结合到HeLa细胞膜上,FA-GNSs会表现出光热效应,利用近红外(NIR)激光以非常低且安全的辐照度进行照射,可在体外杀死相同的细胞。因此,我们证明按照上述方法设计的FA-GNSs是治疗诊断型纳米器件的一种有效原型。