Key Laboratory of Coastal Zone Environmental Processes, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences (CAS), YICCAS, Yantai Shandong 264003, 17 Chunhui Road, Yantai 264003, PR China.
Chemistry. 2012 May 7;18(19):5935-43. doi: 10.1002/chem.201103571. Epub 2012 Mar 29.
Herein, we report the synthesis of biocompatible triplex Ag@SiO(2)@mTiO(2) core-shell nanoparticles (NPs) for simultaneous fluorescence-surface-enhanced Raman scattering (F-SERS) bimodal imaging and drug delivery. Stable Raman signals were created by typical SERS tags that were composed of Ag NPs for optical enhancement, a reporter molecule of 4-mercaptopyridine (4-Mpy) for a spectroscopic signature, and a silica shell for protection. A further coating of mesoporous titania (mTiO(2)) on the SERS tags offered high loading capacity for a fluorescence dye (flavin mononucleotide) and an anti-cancer drug (doxorubicin (DOX)), thereby endowing the material with fluorescence-imaging and therapeutic functions. The as-prepared F-SERS dots exhibited strong fluorescence when excited by light at 460 nm whilst a stable, characteristic 4-Mpy SERS signal was detected when the excitation wavelength was changed to longer wavelength (632.8 nm), both in solution and after incorporation inside living cells. Their excellent biocompatibility was demonstrated by low cytotoxicity against MCF-7 cells, even at a high concentration of 100 μg mL(-1). In vitro cell cytotoxicity confirmed that DOX-loaded F-SERS dots had a comparable or even greater therapeutic effect compared with the free drug, owing to the increased cell-uptake, which was attributed to the possible endocytosis mechanism of the NPs. To the best of our knowledge, this is the first proof-of-concept investigation on a multifunctional nanomedicine that possessed a combined capacity for fast and multiplexed F-SERS labeling as well as drug-loading for cancer therapy.
在此，我们报告了生物相容性的三聚体 Ag@SiO(2)@mTiO(2) 核壳纳米粒子（NPs）的合成，用于同时进行荧光-表面增强拉曼散射（F-SERS）双模式成像和药物输送。典型的 SERS 标记物通过 Ag NPs 产生稳定的拉曼信号，用于光学增强、4-巯基吡啶（4-Mpy）报告分子用于光谱特征以及二氧化硅壳用于保护。在 SERS 标记物上进一步涂覆介孔二氧化钛（mTiO(2)），为荧光染料（黄素单核苷酸）和抗癌药物（阿霉素（DOX））提供了高负载能力，从而使该材料具有荧光成像和治疗功能。当用 460nm 的光激发时，所制备的 F-SERS 点表现出强荧光，而当激发波长改变为更长波长（632.8nm）时，在溶液中和在活细胞内掺入后，都可以检测到稳定的特征 4-Mpy SERS 信号。它们对 MCF-7 细胞的低细胞毒性证明了它们的优异生物相容性，即使在 100μg mL(-1)的高浓度下也是如此。体外细胞毒性证实，负载 DOX 的 F-SERS 点与游离药物相比具有相当或甚至更大的治疗效果，这归因于 NPs 的可能内吞作用机制导致细胞摄取增加。据我们所知，这是首例关于多功能纳米医学的概念验证研究，该纳米医学具有快速和多重 F-SERS 标记以及用于癌症治疗的药物负载的综合能力。
