Qi Lifeng, Gao Xiaohu
Department of Bioengineering, University of Washington, William H. Foege Building N530M, Campus Box 355061, Seattle, Washington 98195, USA.
ACS Nano. 2008 Jul;2(7):1403-10. doi: 10.1021/nn800280r.
A new generation of nanoparticle carrier that allows efficient delivery and real-time imaging of siRNA in live cells has been developed by combining two distinct types of nanomaterials, semiconductor quantum dots and amphipols. An important finding is that, although amphipols are broadly used for solubilizing and delivering hydrophobic proteins into the lipid bilayers of cell membrane, when combined with nanoparticles, they offer previously undiscovered functionalities, including cytoplasm delivery, siRNA protection, and endosome escape. Compared with the classic siRNA carriers such as Lipofectamine and polyethyleneimine, this new class of nanocarrier works in both serum-free and complete cell culture media, which is advantageous over Lipofectamine. It also outperforms polyethyleneimine in gene silencing under both conditions with significantly reduced toxicity. Furthermore, the intrinsic fluorescence of quantum dots provides a mechanism for real-time imaging of siRNA delivery in live cells. This new multifunctional, compact, and traceable nanocarrier is expected to yield important information on rational design of siRNA carriers and to have widespread applications of siRNA delivery and screening in vitro and in vivo.
通过结合两种不同类型的纳米材料——半导体量子点和两性离子两亲分子,已经开发出一种新一代纳米颗粒载体,它能够在活细胞中实现小干扰RNA(siRNA)的高效递送和实时成像。一个重要的发现是,尽管两性离子两亲分子广泛用于将疏水蛋白质溶解并递送至细胞膜的脂质双层中,但当与纳米颗粒结合时,它们会展现出此前未被发现的功能,包括细胞质递送、siRNA保护和内体逃逸。与经典的siRNA载体如脂质体转染试剂和聚乙烯亚胺相比,这类新型纳米载体在无血清和完全细胞培养基中均能发挥作用,这一点优于脂质体转染试剂。在这两种条件下,它在基因沉默方面也优于聚乙烯亚胺,且毒性显著降低。此外,量子点的固有荧光为活细胞中siRNA递送的实时成像提供了一种机制。这种新型多功能、紧凑且可追踪的纳米载体有望为siRNA载体的合理设计提供重要信息,并在体外和体内的siRNA递送及筛选中得到广泛应用。