Cell-penetrating peptides (CPPs) are capable of delivering membrane-impermeable cargoes (including small molecules, peptides, proteins, nucleic acids, and nanoparticles) into the cytosol of mammalian cells and have the potential to revolutionize biomedical research and drug discovery. However, the mechanism of action of CPPs has remained poorly understood, especially how they escape from the endosome into the cytosol following endocytic uptake. We show herein that CPPs exit the endosome by inducing budding and collapse of CPP-enriched vesicles from the endosomal membrane. This mechanism provides a theoretical basis for designing CPPs and other delivery vehicles of improved efficiencies.

中文翻译：

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细胞穿透肽通过诱导囊泡出芽和塌陷逃离内体。

细胞穿透肽 (CPP) 能够将不透膜的货物（包括小分子、肽、蛋白质、核酸和纳米颗粒）输送到哺乳动物细胞的细胞质中，并有可能彻底改变生物医学研究和药物发现。然而，CPPs 的作用机制仍然知之甚少，尤其是它们如何在内吞吸收后从内体逃逸到细胞质中。我们在本文中表明，CPP 通过诱导富含 CPP 的囊泡从内体膜出芽和塌陷而离开内体。该机制为设计 CPP 和其他提高效率的运载工具提供了理论基础。