University Medical Center Groningen, University of Groningen, Department of Cell Biology, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
J Control Release. 2013 Feb 28;166(1):46-56. doi: 10.1016/j.jconrel.2012.12.014. Epub 2012 Dec 20.
Cationic lipid- and polymer-based nanodevices are considered appropriate alternatives for virus-based particles for delivery of nucleic acids, including genes and siRNA, into eukaryotic cells. Because of colloidal stability concerns and toxicity issues the potential in vivo application of these so-called non-viral systems, in particular cationic lipids, was met with considerable skepticism. However, in recent years, the development of novel ionizable cationic lipid formulations in conjunction with sophisticated procedures to carefully control the size of the nanoparticles has rapidly advanced options for a successful therapeutic application. Thus it would appear that cationic lipids have taken a prominent step ahead in their potential use as nanocarriers for siRNA delivery in gene silencing of target genes in a variety of diseases. Verification and improvement of delivery efficiency as well as screening of targeting ligands justify further work in revealing underlying mechanisms that are instrumental in efficient crossing of cellular barriers by cationic lipid-based nanocarriers. In this regard, triggering entry into specific pathways or modulating trafficking along such pathways, either by targeting of nanoparticles or by affecting specific cellular signaling pathways, may represent promising tools. Such options may involve, for example, facilitating nanoparticle transport across endothelial cells by transcytotic mechanisms, or improving delivery efficiency by affecting nanoparticle trafficking that avoids lysosomal delivery. Here, recent progress in the field of lipid-based nanocarriers is discussed, with a focus on mechanisms underlying their interactions with cells in vitro. Where appropriate, we will include mechanisms for polymer-based systems in our discussion.
阳离子脂质体和聚合物纳米器件被认为是基于病毒颗粒的替代物，可将核酸（包括基因和 siRNA）递送至真核细胞。由于胶体稳定性问题和毒性问题，这些所谓的非病毒系统（尤其是阳离子脂质体）的潜在体内应用受到了相当大的质疑。然而，近年来，新型可离子化阳离子脂质体制剂的开发，结合精心控制纳米颗粒大小的复杂程序，迅速推进了成功治疗应用的选择。因此，阳离子脂质体似乎在作为纳米载体将 siRNA 递送至各种疾病的靶基因的基因沉默方面迈出了重要的一步。验证和提高递送效率以及筛选靶向配体，证明了进一步揭示阳离子脂质体纳米载体有效穿过细胞屏障的基础机制的工作是合理的。在这方面，通过靶向纳米颗粒或影响特定细胞信号通路，触发进入特定途径或调节沿着这些途径的运输，可能是有前途的工具。例如，这些选择可能涉及通过胞吞作用机制促进纳米颗粒穿过内皮细胞的运输，或者通过影响避免溶酶体递送的纳米颗粒运输来提高递送效率。本文讨论了基于脂质的纳米载体领域的最新进展，重点介绍了它们与细胞体外相互作用的机制。在适当的情况下，我们将在讨论中包括聚合物基系统的机制。
