Betker Jamie L, Kullberg Max, Gomez Joe, Anchordoquy Thomas J
University of Colorado Denver, Skaggs School of Pharmacy & Pharmaceutical Sciences, Aurora, CO 80045, USA.
Ther Deliv. 2013 Apr;4(4):453-62. doi: 10.4155/tde.13.16.
The formation of cholesterol domains in lipoplexes has been associated with enhanced serum stability and transfection rates both in cell culture and in vivo.
This study utilizes the ability of saturated phosphatidylcholines to promote the formation of cholesterol domains at much lower cholesterol contents than have been utilized in previous work. The results demonstrate that lipoplexes with identical cholesterol and cationic lipid contents exhibit significantly improved transfection efficiencies when a domain is present, consistent with previous work. In addition, studies assessing transfection rates in the absence of serum demonstrate that the ability of domains to enhance transfection is not dependent on interactions with serum proteins. Consistent with this hypothesis, characterization of the adsorbed proteins composing the corona of these lipoplex formulations did not reveal a correlation between transfection and the adsorption of a specific protein.
We have demonstrated that the interaction with serum proteins can promote domain formation in some formulations, and thereby result in enhanced transfection only after serum exposure.
脂质体中胆固醇结构域的形成与细胞培养和体内增强的血清稳定性及转染率相关。
本研究利用饱和磷脂酰胆碱在比以往工作中更低的胆固醇含量下促进胆固醇结构域形成的能力。结果表明，具有相同胆固醇和阳离子脂质含量的脂质体在存在结构域时表现出显著提高的转染效率，这与先前的工作一致。此外，在无血清情况下评估转染率的研究表明，结构域增强转染的能力不依赖于与血清蛋白的相互作用。与此假设一致，对构成这些脂质体制剂冠层的吸附蛋白的表征未揭示转染与特定蛋白吸附之间的相关性。
我们已经证明，与血清蛋白的相互作用可在某些制剂中促进结构域形成，从而仅在血清暴露后导致转染增强。
