Chitosan-Mangafodipir nanoparticles designed for intranasal delivery of siRNA and DNA to brain.
Chitosan-Mangafodipir nanoparticles designed for intranasal delivery of siRNA and DNA to brain.
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DOI：
10.1016/j.jddst.2017.11.013
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发表时间：
2018-03
影响因子：
5
通讯作者：
Sava V
中科院分区：
文献类型：
--
作者：
Sanchez-Ramos J;Song S;Kong X;Foroutan P;Martinez G;Dominguez-Viqueria W;Mohapatra S;Mohapatra S;Haraszti RA;Khvorova A;Aronin N;Sava V
本研究的总体目标是开发一种纳米载体系统，用于非侵入性地将用于基因治疗的分子递送至大脑。在小鼠成纤维细胞的eGFP表达细胞系（NIH3T3）的细胞培养物中测试携带抗eGFP siRNA的含锰纳米颗粒（mNP）。然后在小鼠体内测试最佳mNP。鼻内滴注后，在24和48小时通过7T MRI在整个脑中可视化mNP。mNP有效地显著降低Tg GFP+小鼠中嗅球、纹状体、海马和皮质中的GFP mRNA表达。鼻内滴注装载有编码RFP的dsDNA的mesenchymal也导致RFP在多个脑区域中的表达。总之，携带siRNA或dsDNA的mNP能够将有效载荷从鼻递送至脑。这种将基因疗法传递给人类的方法如果成功，将对神经退行性疾病的疾病修饰疗法产生重大影响。
The overall objective of the present research was to develop a nanocarrier system for non-invasive delivery to brain of molecules useful for gene therapy. Manganese-containing nanoparticles (mNPs) carrying anti-eGFP siRNA were tested in cell cultures of eGFP-expressing cell line of mouse fibroblasts (NIH3T3). The optimal mNPs were then tested in vivo in mice. Following intranasal instillation, mNPs were visualized by 7T MRI throughout brain at 24 and 48 hrs. mNPs were effective in significantly reducing GFP mRNA expression in Tg GFP+ mice in olfactory bulb, striatum, hippocampus and cortex. Intranasal instillation of mNPS loaded with dsDNA encoding RFP also resulted in expression of the RFP in multiple brain regions. In conclusion, mNPs carrying siRNA, or dsDNA were capable of delivering the payload from nose to brain. This approach for delivery of gene therapies to humans, if successful, will have a significant impact on disease-modifying therapeutics of neurodegenerative diseases.
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影响因子：
16.2
作者：
Kordasiewicz HB;Stanek LM;Wancewicz EV;Mazur C;McAlonis MM;Pytel KA;Artates JW;Weiss A;Cheng SH;Shihabuddin LS;Hung G;Bennett CF;Cleveland DW
通讯作者：
Cleveland DW
DOI：
10.1073/pnas.0500195102
发表时间：
2005-03-08
影响因子：
11.1
作者：
De Rosa, R;Garcia, AA;Cattaneo, A
通讯作者：
Cattaneo, A
影响因子：
5
作者：
Karlsson, Jan Olof G.;Adolfsson, Karin;Falkmer, Ursula G.
通讯作者：
Falkmer, Ursula G.
影响因子：
7.4
作者：
Sava, V;Mosquera, D;Sánchez-Ramos, JR
通讯作者：
Sánchez-Ramos, JR
影响因子：
48
作者：
Marks, William J., Jr.;Bartus, Raymond T.;Olanow, C. Warren
通讯作者：
Olanow, C. Warren