The Cysteine-Containing Cell-Penetrating Peptide AP Enables Efficient Macromolecule Delivery to T Cells and Controls Autoimmune Encephalomyelitis

Kim, Won-Ju; Kim, Gil-Ran; Cho, Hyun-Jung; Choi, Je-Min

doi:10.3390/pharmaceutics13081134

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The Cysteine-Containing Cell-Penetrating Peptide AP Enables Efficient Macromolecule Delivery to T Cells and Controls Autoimmune Encephalomyelitis

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Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Korea

Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea

Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul 04763, Korea

Author to whom correspondence should be addressed.

Academic Editors: Evgenia G. Korzhikova-Vlakh and Ivan Guryanov

Pharmaceutics 2021, 13(8), 1134; https://doi.org/10.3390/pharmaceutics13081134

Received: 8 June 2021 / Revised: 17 July 2021 / Accepted: 22 July 2021 / Published: 25 July 2021

(This article belongs to the Special Issue Advances in Delivering Protein and Peptide Therapeutics)

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Abstract

T cells are key immune cells involved in the pathogenesis of several diseases, rendering them important therapeutic targets. Although drug delivery to T cells is the subject of continuous research, it remains challenging to deliver drugs to primary T cells. Here, we used a peptide-based drug delivery system, AP, which was previously developed as a transdermal delivery peptide, to modulate T cell function. We first identified that AP-conjugated enhanced green fluorescent protein (EGFP) was efficiently delivered to non-phagocytic human T cells. We also confirmed that a nine-amino acid sequence with one cysteine residue was the optimal sequence for protein delivery to T cells. Next, we identified the biodistribution of AP-dTomato protein in vivo after systemic administration, and transduced it to various tissues, such as the spleen, liver, intestines, and even to the brain across the blood–brain barrier. Next, to confirm AP-based T cell regulation, we synthesized the AP-conjugated cytoplasmic domain of CTLA-4, AP-ctCTLA-4 peptide. AP-ctCTLA-4 reduced IL-17A expression under Th17 differentiation conditions in vitro and ameliorated experimental autoimmune encephalomyelitis, with decreased numbers of pathogenic IL-17A⁺GM-CSF⁺ CD4 T cells. These results collectively suggest the AP peptide can be used for the successful intracellular regulation of T cell function, especially in the CNS. View Full-Text

Keywords: T cell; immune regulation; cell-penetrating peptide; AP; CTLA-4; multiple sclerosis; experimental autoimmune encephalomyelitis EAE; drug delivery system

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MDPI and ACS Style

Kim, W.-J.; Kim, G.-R.; Cho, H.-J.; Choi, J.-M. The Cysteine-Containing Cell-Penetrating Peptide AP Enables Efficient Macromolecule Delivery to T Cells and Controls Autoimmune Encephalomyelitis. Pharmaceutics 2021, 13, 1134. https://doi.org/10.3390/pharmaceutics13081134

AMA Style

Kim W-J, Kim G-R, Cho H-J, Choi J-M. The Cysteine-Containing Cell-Penetrating Peptide AP Enables Efficient Macromolecule Delivery to T Cells and Controls Autoimmune Encephalomyelitis. Pharmaceutics. 2021; 13(8):1134. https://doi.org/10.3390/pharmaceutics13081134

Chicago/Turabian Style

Kim, Won-Ju, Gil-Ran Kim, Hyun-Jung Cho, and Je-Min Choi. 2021. "The Cysteine-Containing Cell-Penetrating Peptide AP Enables Efficient Macromolecule Delivery to T Cells and Controls Autoimmune Encephalomyelitis" Pharmaceutics 13, no. 8: 1134. https://doi.org/10.3390/pharmaceutics13081134

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The Cysteine-Containing Cell-Penetrating Peptide AP Enables Efficient Macromolecule Delivery to T Cells and Controls Autoimmune Encephalomyelitis

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