Fig. 5: Schematic illustration of intracellular delivery mediated by eTAT and other TAT-based methods. | Nature Communications

Fig. 5: Schematic illustration of intracellular delivery mediated by eTAT and other TAT-based methods.

From: Efficient intracellular delivery of proteins by a multifunctional chimaeric peptide in vitro and in vivo

Fig. 5: Schematic illustration of intracellular delivery mediated by eTAT and other TAT-based methods.The alternative text for this image may have been generated using AI.

a The first step of intracellular delivery is the electrostatic interaction between TAT and membrane components on the cell surface (e.g. glycosaminoglycans), and then, cargos are internalised via TAT-induced endocytosis. However, T-cargos are entrapped in endosomes, and the majority of the cargo is ultimately targeted to lysosomes for degradation. b Even when the endosomal membrane is disrupted by INF7 (TI-Cargo), the majority of the cargo remains entrapped in endosomes because of the interaction between the endosomal membrane and TAT and/or that between the endosomal membrane and INF7. c When the proteolytic sites N and Ne are cleaved by endosome-localised proteases cathepsin and furin, the cargo is separated from TAT-INF7 and released rapidly from the disrupted endosome (TINNe-Cargo) into the cytosol. d, e The leucine zipper (LZ) can induce the formation of homodimers of the eTAT-cargo (TINNeL-cargo), which results in improved endocytosis (d) and weakened competitiveness of serum protein albumin (e) via increased local concentration of TAT that can interact with the cellular membrane components. CTSL: cathepsin L.

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