College of Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.
School of Science, Constructor University, Bremen 28759, Germany.
Proc Natl Acad Sci U S A. 2024 Oct 29;121(44):e2407515121. doi: 10.1073/pnas.2407515121. Epub 2024 Oct 22.
Intracellular protein delivery has the potential to revolutionize cell-biological research and medicinal therapy, with broad applications in bioimaging, disease treatment, and genome editing. Herein, we demonstrate successful delivery of a functional protein, cytochrome c (CYC), by using a boron cluster anion as molecular carrier of the superchaotropic anion type (BBrOPr). CYC was delivered into lipid bilayer vesicles as well as living cells, with a cellular uptake ratio approaching 90%. Mechanistic studies showed that CYC was internalized into cells through a permeation pathway directly into the cytoplasm, bypassing endosomal entrapment. Upon carrier-assisted internalization, CYC retained its bioactivity, as reflected by an induced cell apoptosis rate of 25% at low dose (1 µM). This study furbishes a direct protein delivery method by a molecular carrier with high efficiency, confirming the potential of inorganic cluster ions as protein transport vehicles with an extensive range of future cell-biological or biomedical applications.
细胞内蛋白质递送有可能彻底改变细胞生物学研究和医学治疗，在生物成像、疾病治疗和基因组编辑方面有着广泛的应用。在此，我们展示了一种功能性蛋白质细胞色素 c（CYC）的成功递送，使用硼簇阴离子作为超离域阴离子型（BBrOPr）的分子载体。CYC 被递送到脂质双层囊泡和活细胞中，细胞摄取率接近 90%。机理研究表明，CYC 通过一种直接进入细胞质的渗透途径进入细胞，绕过了内体捕获。在载体辅助内化后，CYC 保持其生物活性，低剂量（1 μM）时诱导细胞凋亡率为 25%。这项研究提供了一种高效的分子载体直接递送蛋白质的方法，证实了无机簇离子作为具有广泛未来细胞生物学或生物医学应用的蛋白质运输载体的潜力。
