Construction of Novel Brain-Targeting Gene Delivery System by Natural Magnetic Nanoparticles
Construction of Novel Brain-Targeting Gene Delivery System by Natural Magnetic Nanoparticles
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DOI：
10.1002/app.33995
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发表时间：
2011-09-15
影响因子：
3
通讯作者：
Chang, Jin
中科院分区：
文献类型：
--
作者：
Han, Lei;Zhang, Anling;Chang, Jin
脑肿瘤基因治疗的主要目标是开发高效、低毒、脑靶向的基因传递系统，使其能够穿过血脑屏障（BBB）将治疗基因传递到脑癌组织。在这项研究中，我们首次设计并构建了一种新的基因传递系统（Tat-MS-PAMAM），该系统是用聚胺胺（PAMAM）树状大分子和Tat肽修饰磁小体（MS）。利用体外U251人胶质瘤细胞，研究了tk - ms - pamam与荧光素酶报告质粒（pGL-3）容易形成多聚体，提高了质粒对多阴离子和dna酶i的络合性和稳定性。结果表明，外加磁场与Tat肽的结合可显著提高传递体系的转染效率。此外，体内生物分布表明，Tat-MS-PAMAM可以有效地通过血脑屏障运输并在单光子发射计算机断层扫描检测到的大鼠脑组织中组装。因此，Tat-MS-PAMAM具有磁靶向、血脑屏障转运和高效基因转染的多重功能，可能成为脑肿瘤基因治疗的一种新型非病毒递送系统。(C) 2011 Wiley期刊公司应用化学学报，2011,31 (2):444 - 444
The main objective in gene therapy of brain tumors is to develop efficient, low toxic, and brain-targeting gene delivery systems which can cross the blood-brain barrier (BBB) and deliver therapeutic gene to the brain cancerous tissues. In this study, we designed and constructed a novel gene delivery systems (Tat-MS-PAMAM) by modifying the magnetosome (MS) with polyamidoamine (PAMAM) dendrimers and Tat peptides for the first time. Tat-MS-PAMAM readily formed polyplexes with the luciferase reporter plasmid (pGL-3) and improved plasmid complexation and stability against polyanion and DNase I. Transfection efficiencies of Tat-MS-PAMAM polyplexes with pGL-3 were studied using U251 human glioma cells in vitro. The result showed that the incorporation of external magnetic field and Tat peptides could significantly improve transfection efficiency of delivery system. Furthermore, biodistribution in vivo demonstrated that Tat-MS-PAMAM could efficiently transport across the BBB and assemble at brain tissue of rat detected by single photo emission computed tomography. Thus, with the multifunction of magnetic targeting, BBB transporting, and efficient gene transfecting, Tat-MS-PAMAM might be a novel nonviral delivery system for gene therapy of brain tumors. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 3446-3454, 2011