Department of Supramolecular & Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, 2300, RA, The Netherlands.
Institute of Biology, Leiden University, Sylviusweg 72, Leiden, 2333, BE, The Netherlands.
Adv Healthc Mater. 2017 Oct;6(20). doi: 10.1002/adhm.201700759. Epub 2017 Sep 25.
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.
蛋白质递送到细胞的细胞质中是纳米医学领域的一个具有挑战性的课题，因为细胞摄取和内涵体逃逸通常效率低下，阻碍了临床应用。在本研究中，使用细胞色素 c（cytC）作为模型膜不可渗透蛋白，研究了含有大孔径（10nm）盘状空腔的立方介孔硅纳米颗粒（MSNs）作为蛋白质递药载体。为了确保胶体稳定性，MSNs 用融合脂质双层（LB）进行包覆，并通过互补的卷曲螺旋（CC）肽诱导细胞摄取。卷曲螺旋诱导的膜融合导致 cytC 的有效细胞质递送，并触发细胞凋亡。在存在各种内吞抑制剂的情况下，LB 包覆 MSNs 的递送强烈表明膜融合是细胞摄取的主要机制。该方法可能是通过 CC 诱导的膜融合将任何类型的无机纳米颗粒或蛋白质高效递送到细胞中的通用方法。
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