1. Hydroxyl-Rich Hydrophilic Endocytosis-Promoting Peptide with No Positive Charge.
- Author
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Wang S, Li Z, Aispuro D, Guevara N, Van Valkenburgh J, Chen B, Zhou X, McCarroll MN, Ji F, Cong X, Sarkar P, Chaudhuri R, Guo Z, Perkins NP, Shao S, Sello JK, Chen K, and Xue M
- Subjects
- Animals, Endosomes metabolism, Lysosomes metabolism, Hydrophobic and Hydrophilic Interactions, Endocytosis, Cell-Penetrating Peptides metabolism
- Abstract
Delivering cargo molecules across the plasma membrane is critical for biomedical research, and the need to develop molecularly well-defined tags that enable cargo transportation is ever-increasing. We report here a hydrophilic endocytosis-promoting peptide (EPP6) rich in hydroxyl groups with no positive charge. EPP6 can transport a wide array of small-molecule cargos into a diverse panel of animal cells. Mechanistic studies revealed that it entered the cells through a caveolin- and dynamin-dependent endocytosis pathway, mediated by the surface receptor fibrinogen C domain-containing protein 1. After endocytosis, EPP6 trafficked through early and late endosomes within 30 min. Over time, EPP6 partitioned among cytosol, lysosomes, and some long-lived compartments. It also demonstrated prominent transcytosis abilities in both in vitro and in vivo models. Our study proves that positive charge is not an indispensable feature for hydrophilic cell-penetrating peptides and provides a new category of molecularly well-defined delivery tags for biomedical applications.
- Published
- 2022
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