Niu Shuiqin, Zhang Ling-Kun, Zhang Li, Zhuang Siyi, Zhan Xiuyu, Chen Wu-Ya, Du Shiwei, Yin Liang, You Rong, Li Chu-Hua, Guan Yan-Qing
School of Life Science, South China Normal University, Guangzhou 510631, China.; MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.
School of Life Science, South China Normal University, Guangzhou 510631, China.
Theranostics. 2017 Jan 1;7(2):344-356. doi: 10.7150/thno.16562. eCollection 2017.
Lewy bodies are considered as the main pathological characteristics of Parkinson's disease (PD). The major component of Lewy bodies is α-synuclein (α-syn). The use of gene therapy that targeting and effectively interfere with the expression of α-syn in neurons has received tremendous attention. In this study, we used magnetic FeO nanoparticles coated with oleic acid molecules as a nano-carrier. -isopropylacrylamide derivative (NIPAm-AA) was photo-immobilized onto the oleic acid molecules, and shRNA (short hairpin RNA) was absorbed. The same method was used to absorb nerve growth factor (NGF) to NIPAm-AA to specifically promote neuronal uptake via NGF receptor-mediated endocytosis. Additionally, shRNA plasmid could be released into neurons because of the temperature and pH sensitivity of NIPAm-AA interference with α-syn synthesis. We investigated apoptosis in neurons with abrogated α-syn expression and . The results demonstrated that multifunctional superparamagnetic nanoparticles carrying shRNA for α-syn could provide effective repair in a PD model.
路易小体被认为是帕金森病（PD）的主要病理特征。路易小体的主要成分是α-突触核蛋白（α-syn）。靶向并有效干扰神经元中α-syn表达的基因治疗受到了极大关注。在本研究中，我们使用涂有油酸分子的磁性FeO纳米颗粒作为纳米载体。N-异丙基丙烯酰胺衍生物（NIPAm-AA）被光固定在油酸分子上，并吸附短发夹RNA（shRNA）。采用相同方法将神经生长因子（NGF）吸附到NIPAm-AA上，以通过NGF受体介导的内吞作用特异性促进神经元摄取。此外，由于NIPAm-AA干扰α-syn合成的温度和pH敏感性，shRNA质粒可释放到神经元中。我们研究了α-syn表达缺失的神经元中的细胞凋亡情况。结果表明，携带针对α-syn的shRNA的多功能超顺磁性纳米颗粒可在PD模型中提供有效的修复作用。
