Protein delivery into the cytosol of cells is a challenging topic in the field of nanomedicine, because cellular uptake and endosomal escape are typically inefficient, hampering clinical applications. In this contribution cuboidal mesoporous silica nanoparticles (MSNs) containing disk‐shaped cavities with a large pore diameter (10 nm) are studied as a protein delivery vehicle using cytochrome‐c (cytC) as a model membrane‐impermeable protein. To ensure colloidal stability, the MSNs are coated with a fusogenic lipid bilayer (LB) and cellular uptake is induced by a complementary pair of coiled‐coil (CC) lipopeptides. Coiled‐coil induced membrane fusion leads to the efficient cytosolic delivery of cytC and triggers apoptosis of cells. Delivery of these LB coated MSNs in the presence of various endocytosis inhibitors strongly suggests that membrane fusion is the dominant mechanism of cellular uptake. This method is potentially a universal way for the efficient delivery of any type of inorganic nanoparticle or protein into cells mediated by CC induced membrane fusion.

中文翻译：

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膜融合介导脂质双层包被的介孔二氧化硅纳米粒子的细胞内传递。

在纳米医学领域，将蛋白质递送到细胞质中是一个具有挑战性的课题，因为细胞摄取和内体逃逸通常效率低下，从而妨碍了临床应用。在这项贡献中，使用细胞色素c（cytC）作为膜不透性蛋白的模型，研究了包含大孔径（10 nm）的圆盘形腔的立方形介孔二氧化硅纳米颗粒（MSN）作为蛋白传递载体。为了确保胶体稳定性，MSN涂有融合脂质双层（LB），并且通过一对互补的卷曲螺旋（CC）脂肽诱导细胞摄取。螺旋线圈诱导的膜融合导致cytC的有效胞质传递并触发细胞凋亡。在各种内吞抑制剂的存在下这些LB包被的MSN的传递强烈表明膜融合是细胞摄取的主要机制。该方法潜在地是将任何类型的无机纳米颗粒或蛋白质有效递送到由CC诱导的膜融合介导的细胞中的通用方法。