Intracellular Delivery of Antisense Peptide Nucleic Acid by Fluorescent Mesoporous Silica Nanoparticles

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• 作者：Xing Ma ; Gitali Devi ; Qiuyu Qu ; Desiree-Faye Kaixin Toh ; Gang Chen ; Yanli Zhao
• 刊名：Bioconjugate Chemistry
• 出版年：2014
• 出版时间：August 20, 2014
• 年：2014
• 卷：25
• 期：8
• 页码：1412-1420
• 全文大小：494K
• ISSN：1520-4812

文摘

In order to overcome poor cell permeability of antisense peptide nucleic acid (PNA), a fluorescent mesoporous silica nanoparticle (MSNP) carrier was developed to successfully deliver antisense PNA into cancer cells for effective silence of B-cell lymphoma 2 (Bcl-2) protein expression in vitro. First, fluorescent MSNP functionalized with disulfide bond bridged groups was fabricated and characterized. Antisense and negative control PNAs were synthesized and further conjugated with fluorescent dye cyanine 5. Then, the PNAs were covalently connected with fluorescent MSNP via amidation between amino group of PNAs and carboxylic acid group on the MSNP surface. High intracellular concentration of glutathione serves as a natural reducing agent, which could cleave the disulfide bond to trigger the PNA release in vitro. Confocal laser scanning microscopy studies prove that PNA conjugated MSNP was endocytosed by HeLa cancer cells, and redox-controlled intracellular release of antisense PNA from fluorescent MSNP was successfully achieved. Finally, effective silencing of the Bcl-2 protein expression induced by the delivered antisense PNA into HeLa cells was confirmed by Western blot assay.