PDF(Pubmed)
Abstract：
The membrane-fusion-based internalization without lysosomal entrapment is advantageous for intracellular delivery over endocytosis. However, protein corona formed on the membrane-fusogenic liposome surface converts its membrane-fusion performance to lysosome-dependent endocytosis, causing poorer delivery efficiency in biological conditions. Herein, we develop an antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo. Leveraging specific lipid composition at an optimized ratio, such antifouling membrane-fusogenic liposome facilitates fusion capacity even in protein-rich conditions, attributed to the copious zwitterionic phosphorylcholine groups for protein-adsorption resistance. Consequently, the antifouling membrane-fusogenic liposome demonstrates robust membrane-fusion-mediated delivery in the medium with up to 38% fetal bovine serum, outclassing two traditional membrane-fusogenic liposomes effective at 4% and 6% concentrations. When injected into mice, antifouling membrane-fusogenic liposomes can keep their membrane-fusion-transportation behaviors, thereby achieving efficient luciferase transfection and enhancing gene-editing-mediated viral inhibition. This study provides a promising tool for effective intracellular delivery under complex physiological environments, enlightening future nanomedicine design.
摘要：
没有溶酶体截留的基于膜融合的内化对于细胞内递送优于内吞作用是有利的。然而,在膜融合脂质体表面形成的蛋白质冠将其膜融合性能转化为溶酶体依赖性内吞作用，在生物条件下导致较差的递送效率。在这里，我们开发了一种抗污染膜融合脂质体，用于体内有效的细胞内递送。以优化的比例利用特定的脂质组成，这种抗污染膜-融合脂质体即使在富含蛋白质的条件下也能促进融合能力，归因于具有蛋白质吸附抗性的大量两性离子磷酰胆碱基团。因此,抗污染膜融合脂质体在高达38%胎牛血清的培养基中表现出强大的膜融合介导的递送，超越了两种传统的膜融合脂质体，有效浓度为4％和6％。当注射到小鼠体内时，抗污染膜融合脂质体可以保持其膜融合运输行为，从而实现有效的荧光素酶转染和增强基因编辑介导的病毒抑制。这项研究为在复杂的生理环境下有效的细胞内递送提供了一个有希望的工具，启发未来的纳米医学设计。
