Stepwise Orthogonal Click Chemistry toward Fabrication of Paclitaxel/Galactose Functionalized Fluorescent Nanoparticles for HepG2 Cell Targeting and Delivery

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• 作者：Chian-Hui Lai ; Tsung-Che Chang ; Yung-Jen Chuang ; Der-Lii Tzou ; Chun-Cheng Lin
• 刊名：Bioconjugate Chemistry
• 出版年：2013
• 出版时间：October 16, 2013
• 年：2013
• 卷：24
• 期：10
• 页码：1698-1709
• 全文大小：609K
• 年卷期：v.24,no.10(October 16, 2013)
• ISSN：1520-4812

文摘

In this report, we used stepwise orthogonal click chemistry (SOCC) involving strain-promoted azide鈥揳lkyne cycloaddition (SPAAC) and microwave-assisted Cu(I)-catalyzed azide鈥揳lkyne cycloaddition (CuAAC) to assemble an anticancer drug (paclitaxel, PTX) and a targeting ligand (trivalent galactoside, TGal) on a fluorescent silicon oxide nanoparticle (NP) by using dialkyne linker 8 as a bridge. The fluorescent NH₂@Cy3SiO₂NP was fabricated using a competition method to incorporate Cy3 without loss of the original surface amine density on the NPs. The concept of SOCC was first investigated in a solution-phase model study that showed quantitative reaction yield. In the fabrication of TGal-PTX@Cy3SiO₂NP, the expensive compound azido-functionalized PTX 12 used in SPAAC can be easily recovered due to the absence of other reagents in the reaction mixture. High loading of the sugar ligand on the NP surface serves a targeting function and also overcomes the low water solubility of PTX. Confocal fluorescence microscopy and cytotoxicity assay showed that TGal-PTX@Cy3SiO₂NP was taken up by HepG2 cells and was affected by the microtubule skeleton in these cells and inhibited the proliferation of these cells in a dose-dependent manner. The presence of a fluorescent probe, a targeting ligand, and an anticancer drug on the multifunctional TGal-PTX@Cy3SiO₂NP allows for real-time imaging, specific cancer-cell targeting, and the cell-killing effect which is better than free PTX.