Design of novel cell penetrating peptides for the delivery of trehalose into mammalian cells

•A novel cell penetrating peptide (CPP) was designed based on molecular simulations.•The CPP has high efficiency of penetrating into cells with little cytotoxicity.•Trehalose can be specifically delivered into cells with high efficiency.

Stabilization of cells in a desiccated state can significantly simplify the storage and transportation and save expenses for clinical applications. Introduction of the impermeable disaccharide, trehalose, into cells is an important step to improve the desiccation tolerance of cells. In this study, a novel cell penetrating peptide, KRKRWHW, was developed based on molecular simulations. The peptide exhibited little cytotoxicity and high penetrating efficiency into mammalian cells. The cell viability of mouse embryonic fibroblasts (MEFs) after the incubation with various concentrations of KRKRWHW from 0.01 mM to 5 mM at 37 °C for 4 h was maintained at around 100%. The peptide was able to penetrate into MEFs within 1 h at 37 °C with an efficiency of around 90% at 0.1 mM. Trehalose, as a cargo coupled with the peptide of KRKRWHW through hydrogen bond and π–π bond, was successfully loaded into the MEFs. This novel peptide provides a novel approach for the delivery of trehalose into mammalian cells.

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