Milogrodzka Izabela, Nguyen Pham Duy Tue, Sama Gopal R, Samadian Hajar, Zhai Jiali, de Campo Liliana, Kirby Nigel M, Scott Timothy F, Banaszak Holl Mark M, van 't Hag Leonie
Department of Chemical and Biological Engineering, Monash University, Clayton, VIC 3800, Australia.
School of Science, STEM College, RMIT University, Melbourne, VIC 3000, Australia.
ACS Nano. 2023 May 9;17(9):8598-8612. doi: 10.1021/acsnano.3c01095. Epub 2023 Apr 20.
Biomimetic cubic phases can be used for protein encapsulation in a variety of applications such as biosensors and drug delivery. Cubic phases with a high concentration of cholesterol and phospholipids were obtained herein. It is shown that the cubic phase structure can be maintained with a higher concentration of biomimetic membrane additives than has been reported previously. Opposing effects on the curvature of the membrane were observed upon the addition of phospholipids and cholesterol. Furthermore, the coronavirus fusion peptide significantly increased the negative curvature of the biomimetic membrane with cholesterol. We show that the viral fusion peptide can undergo structural changes leading to the formation of hydrophobic α-helices that insert into the lipid bilayer. This is of high importance, as a fusion peptide that induces increased negative curvature as shown by the formation of inverse hexagonal phases allows for greater contact area between two membranes, which is required for viral fusion to occur. The cytotoxicity assay showed that the toxicity toward HeLa cells was dramatically decreased when the cholesterol or peptide level in the nanoparticles increased. This suggests that the addition of cholesterol can improve the biocompatibility of the cubic phase nanoparticles, making them safer for use in biomedical applications. As the results, this work improves the potential for the biomedical end-use applications of the nonlamellar lipid nanoparticles and shows the need of systematic formulation studies due to the complex interplay of all components.
仿生立方相可用于多种应用中的蛋白质封装，如生物传感器和药物递送。本文制备了具有高浓度胆固醇和磷脂的立方相。结果表明，与先前报道相比，在更高浓度的仿生膜添加剂存在下，立方相结构仍可维持。添加磷脂和胆固醇时，观察到对膜曲率的相反影响。此外，冠状病毒融合肽显著增加了含胆固醇仿生膜的负曲率。我们发现病毒融合肽可发生结构变化，导致形成插入脂质双层的疏水α-螺旋。这一点非常重要，因为如反六角相的形成所示，诱导负曲率增加的融合肽能使两个膜之间有更大的接触面积，而这是病毒融合发生所必需的。细胞毒性试验表明，当纳米颗粒中胆固醇或肽的水平增加时，对HeLa细胞的毒性显著降低。这表明添加胆固醇可改善立方相纳米颗粒的生物相容性，使其在生物医学应用中使用更安全。结果表明，这项工作提高了非层状脂质纳米颗粒在生物医学最终用途应用中的潜力，并表明由于所有成分之间复杂的相互作用，需要进行系统的配方研究。
