Selective Intracellular Delivery of Thiolated Cargo to Tumor and Neovasculature Cells Using Histidine-Rich Peptides as Vectors

J Johannes Eksteen; Dominik Ausbacher; Terje Vasskog; Øystein Rekdal; John S M Svendsen

doi:10.1021/acsomega.9b00700

Selective Intracellular Delivery of Thiolated Cargo to Tumor and Neovasculature Cells Using Histidine-Rich Peptides as Vectors

ACS Omega. 2020 Mar 6;5(10):4937-4942. doi: 10.1021/acsomega.9b00700. eCollection 2020 Mar 17.

Authors

J Johannes Eksteen¹, Dominik Ausbacher², Terje Vasskog¹, Øystein Rekdal³, John S M Svendsen⁴

Affiliations

¹ NORCE Norwegian Research Centre AS, Siva Innovasjonssenter, Sykehusvegen 21, NO 9294 Tromsø, Norway.
² Department of Pharmacy, UiT Arctic University of Norway, NO 9037 Tromsø, Norway.
³ Lytix Biopharma AS, Siva Innovasjonssenter, Sykehusvegen 21, P.O. Box 6447, NO 9294 Tromsø, Norway.
⁴ Department of Chemistry, UiT Arctic University of Norway, NO 9037 Tromsø, Norway.

Abstract

Short histidine-rich peptides could serve as novel activatable vectors for delivering cytotoxic payloads to tumor and neovasculature cells. This explorative study reports preliminary results showing that zinc ions, which are found in elevated levels at neovasculature sites, can trigger the intracellular delivery of a short antimicrobial peptide when conjugated to a histidine-rich peptide through a disulfide bond. The importance of exofacial thiols in the mode of action of these disulfide-linked conjugates is also shown.