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用于癌细胞选择性靶向的高度稳定的叶酸功能化铜纳米簇/二氧化硅纳米颗粒。

Highly stable folic acid functionalized copper-nanocluster/silica nanoparticles for selective targeting of cancer cells.

作者信息

Fang Xiaoming, Huang Yanhua, Yu Dan, Shi Caiwen, Liu Ming

机构信息

Department of Respiratory, Affiliated Hospital of Nanjing Medical University, Changzhou Second People's Hospital Changzhou 213003 China

出版信息

RSC Adv. 2020 Aug 26;10(52):31463-31469. doi: 10.1039/d0ra06523d. eCollection 2020 Aug 21.

Abstract

In this paper, we present a novel strategy to construct folic acid functionalized conjugated Cu nanoclusters (CuNCs) and silica (SiO) nanocomposites for targeted detection of cancer cells. First of all, BSA capped CuNCs were encapsulated into a SiO matrix. The resulting CuNCs@SiO nanoparticles showed bright red fluorescence with an enhanced photoluminescence quantum yield compared with free CuNCs, as well as improved stability in a complex biological environment owning to the protection of the SiO matrix. Upon attachment of folic acid the poly-l-lysine conjugates (PLL-FA) on the surface of CuNCs@SiO driven by electrostatic interaction, the as-prepared CuNCs@SiO/PLL-FA nanocomposites are capable of selectively recognizing folate receptor (FR) over-expressed cancer cells rather than FR-negative cells. The cell viability assay proved the low biotoxicity of CuNCs@SiO/PLL-FA nanocomposites toward living cells and the cellular imaging assay results demonstrated their selective endocytosis of FR-positive cells (KB cells), bringing about red fluorescence labeling within the cells. Intriguingly, our strategy provides a novel route to synthesize functional CuNCs@SiO/PLL-FA nanocomposites equipped with superior fluorescence properties, high stability against external stimuli and good biocompatibility, and have great application potential in bioimaging imaging and targeted cell detection.

摘要

在本文中,我们提出了一种构建叶酸功能化共轭铜纳米簇(CuNCs)与二氧化硅(SiO)纳米复合材料的新策略,用于癌细胞的靶向检测。首先,将牛血清白蛋白包覆的CuNCs封装到SiO基质中。所得的CuNCs@SiO纳米颗粒呈现出亮红色荧光,与游离的CuNCs相比,其光致发光量子产率有所提高,并且由于SiO基质的保护,在复杂生物环境中的稳定性也得到改善。通过静电相互作用,将叶酸与聚-L-赖氨酸共轭物(PLL-FA)连接到CuNCs@SiO表面后,所制备的CuNCs@SiO/PLL-FA纳米复合材料能够选择性识别叶酸受体(FR)过表达的癌细胞,而非FR阴性细胞。细胞活力测定证明了CuNCs@SiO/PLL-FA纳米复合材料对活细胞的低生物毒性,细胞成像测定结果表明它们对FR阳性细胞(KB细胞)具有选择性内吞作用,从而在细胞内产生红色荧光标记。有趣的是,我们的策略提供了一条合成具有优异荧光特性、对外部刺激具有高稳定性和良好生物相容性的功能性CuNCs@SiO/PLL-FA纳米复合材料的新途径,并且在生物成像和靶向细胞检测方面具有巨大的应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/003a/9056389/84735a0696cd/d0ra06523d-s1.jpg

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