Qi Lifeng, Shao Weijun, Shi Donglu
Zhejiang California Nanosystems Institute, Zhejiang University, No. 268, Kaixuan Road, Hangzhou, 310029, China.
J Mater Chem B. 2013 Feb 7;1(5):654-660. doi: 10.1039/c2tb00027j. Epub 2012 Nov 26.
In this study, proton-sponge coated quantum dots were prepared by using amphipol PMAL, grafted with polyethylenimine (PEI) as an encapsulation polymer. The QD-PMAL-PEI nanoparticles showed low cytotoxicity and superior gene silencing efficiency in serum-containing medium against junctional adhesion molecule-2 (JAM-2), which is over-expressed in glioma cells. Confocal microscopic analysis showed efficient siRNA intracellular release. In particular, QD-mediated JAM-2 knockdown was reported for the first time to facilitate inhibition of glioma cell migration. Furthermore, the Notch pathway served as the target for the JAM-2 gene function, confirmed by downregulation of its downstream genes HES1 and HES5. The unique proton-sponge coated QDs can serve as multifunctional siRNA carriers for efficient gene silencing and real-time intracellular imaging, and provide a base for design of novel efficient siRNA delivery carriers with high biocompatibility.
在本研究中，通过使用两亲性聚合物PMAL制备质子海绵包覆量子点，该聚合物接枝聚乙烯亚胺（PEI）作为封装聚合物。QD-PMAL-PEI纳米颗粒在含血清培养基中对胶质瘤细胞中过度表达的连接粘附分子-2（JAM-2）显示出低细胞毒性和优异的基因沉默效率。共聚焦显微镜分析显示了有效的siRNA细胞内释放。特别是，首次报道了QD介导的JAM-2基因敲低促进胶质瘤细胞迁移的抑制。此外，Notch信号通路作为JAM-2基因功能的靶点，这通过其下游基因HES1和HES5的下调得到证实。独特的质子海绵包覆量子点可作为多功能siRNA载体，用于高效基因沉默和实时细胞内成像，并为设计具有高生物相容性的新型高效siRNA递送载体提供基础。
