Yang Hong, Li Ying, Li Tingting, Xu Min, Chen Yin, Wu Chunhui, Dang Xitong, Liu Yiyao
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P.R. China.
Division of Trauma, Surgical Critical Care and Burns, University of California San Diego, CA 92103, USA.
Sci Rep. 2014 Nov 17;4:7072. doi: 10.1038/srep07072.
In gene therapy, how genetic therapeutics can be efficiently and safely delivered into target tissues/cells remains a major obstacle to overcome. To address this issue, nanoparticles consisting of non-covalently coupled polyethyleneimine (PEI) and folic acid (FA) to the magnetic and fluorescent core/shell of Fe3O4@SiO2(FITC) was tested for their ability to deliver Notch-1 shRNA. Our results showed that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanoparticles are 64 nm in diameter with well dispersed and superparamagnetic. These nanoparticles with on significant cytotoxicity are capable of delivering Notch-1 shRNA into human breast cancer MDA-MB-231 cells with high efficiency while effectively protected shRNA from degradation by exogenous DNaseI and nucleases. Magnetic resonance (MR) imaging and fluorescence microscopy showed significant preferential uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex by MDA-MB-231 cells. Transfected MDA-MB-231 cells exhibited significantly decreased expression of Notch-1, inhibited cell proliferation, and increased cell apoptosis, leading to the killing of MDA-MB-231 cells. In light of the magnetic targeting capabilities of Fe3O4@SiO2(FITC)/PEI-FA, our results show that by complexing with a second molecular targeting therapeutic, such as Notch-1 shRNA in this report, Fe3O4@SiO2(FITC)/PEI-FA can be exploited as a novel, non-viral, and concurrent targeting delivery system for targeted gene therapy as well as for MR imaging in cancer diagnosis.
在基因治疗中，如何将基因治疗药物高效、安全地递送至靶组织/细胞仍然是一个有待克服的主要障碍。为了解决这一问题，测试了由非共价偶联的聚乙烯亚胺（PEI）和叶酸（FA）与Fe3O4@SiO2（FITC）的磁性和荧光核壳组成的纳米颗粒递送Notch-1 shRNA的能力。我们的结果表明，Fe3O4@SiO2（FITC）/PEI-FA/Notch-1 shRNA纳米颗粒直径为64 nm，分散良好且具有超顺磁性。这些纳米颗粒具有显著的细胞毒性，能够将Notch-1 shRNA高效递送至人乳腺癌MDA-MB-231细胞，同时有效保护shRNA不被外源性DNaseI和核酸酶降解。磁共振（MR）成像和荧光显微镜显示MDA-MB-231细胞对Fe3O4@SiO2（FITC）/PEI-FA/Notch-1 shRNA纳米复合物有显著的优先摄取。转染的MDA-MB-231细胞表现出Notch-1表达显著降低、细胞增殖受到抑制以及细胞凋亡增加，从而导致MDA-MB-231细胞死亡。鉴于Fe3O4@SiO2（FITC）/PEI-FA的磁靶向能力，我们的结果表明，通过与第二种分子靶向治疗剂（如本报告中的Notch-1 shRNA）复合，Fe3O4@SiO2（FITC）/PEI-FA可作为一种新型的、非病毒的、同时具有靶向递送功能的系统，用于靶向基因治疗以及癌症诊断中的MR成像。
