Dipartimento di Chimica, Sapienza Università di Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy.
J Proteomics. 2012 Mar 16;75(6):1924-32. doi: 10.1016/j.jprot.2012.01.003. Epub 2012 Jan 14.
Cationic liposomes (CLs) are one of the most employed nonviral nanovector systems in gene therapy. However, their transfection efficiency is strongly affected by interactions with plasma components, that lead to the formation of a "protein corona" onto CL surface. The interactions between nanoparticles entering the body and biomolecules have an essential role for their biodistribution. Because the knowledge of proteins adsorbed onto vector surface could be useful in the screening of new, more efficient and more biocompatible liposomal formulations, the behavior of three CLs with different membrane charge densities was investigated. The proteins of the three coronas were identified by nano-liquid chromatography-tandem mass spectrometry, and quantified with label-free spectral counting strategy. Fibrinogen displayed higher association with CLs with high membrane charge density, while apolipoproteins and C4b-binding protein with CLs with low membrane charge density. These results are discussed in terms of the different lipid compositions of CLs and may have a deep biological impact for in vivo applications. Surface charge of nanoparticles is emerging as a relevant factor determining the corona composition after interaction with plasma proteins. Remarkably, it is also shown that the charge of the protein corona formed around CLs is strongly related to their membrane charge density.
阳离子脂质体（CL）是基因治疗中最常用的非病毒纳米载体系统之一。然而，它们的转染效率受到与血浆成分相互作用的强烈影响，这导致 CL 表面形成“蛋白质冠”。进入体内的纳米颗粒与生物分子之间的相互作用对其生物分布起着至关重要的作用。由于了解吸附在载体表面上的蛋白质对于筛选新的、更有效和更生物相容的脂质体制剂可能是有用的，因此研究了三种具有不同膜电荷密度的 CL 的行为。通过纳升液相色谱-串联质谱法鉴定了三种冠层中的蛋白质，并使用无标记谱计数策略进行定量。纤维蛋白原与高膜电荷密度的 CL 结合更高，而载脂蛋白和 C4b 结合蛋白与低膜电荷密度的 CL 结合。根据 CL 的不同脂质组成讨论了这些结果，并且可能对体内应用具有深刻的生物学影响。纳米颗粒的表面电荷在与血浆蛋白相互作用后成为决定冠层组成的相关因素。值得注意的是，还表明围绕 CL 形成的蛋白质冠的电荷与它们的膜电荷密度密切相关。
