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Comb-like pseudopeptides enable very rapid and efficient intracellular trehalose delivery for enhanced cryopreservation of erythrocytes

Title: Comb-like pseudopeptides enable very rapid and efficient intracellular trehalose delivery for enhanced cryopreservation of erythrocytes
Authors: Chen, S
Wu, L
Ren, J
Bemmer, VL
Zajicek, R
Chen, R
Item Type: Journal Article
Abstract: Cell cryopreservation plays a key role in development of reproducible and cost-effective cell-based therapies. Trehalose accumulated in freezing and desiccation tolerant organisms in nature has been sought as an attractive non-toxic cryoprotectant. Herein, we report a co-incubation method for very rapid and efficient delivery of membrane-impermeable trehalose into ovine erythrocytes through reversible membrane permeabilization using pH-responsive, comb-like pseudopeptides. The pseudopeptidic polymers containing relatively long alkyl side chains were synthesized to mimic membrane-anchoring fusogenic proteins. The intracellular trehalose delivery efficiency was optimized by manipulating the side chain length, degree of substitution and concentration of the pseudopeptides with different hydrophobic alkyl side chains, the pH, temperature and time of incubation, as well as the polymer-to-cell ratio and the concentration of extracellular trehalose. Treatment of erythrocytes with the comb-like pseudopeptides for only 15 min yielded an intracellular trehalose concentration of 177.9 ± 8.6 mM, which resulted in 90.3 ± 0.7% survival after freeze-thaw. The very rapid and efficient delivery was found to be attributed to the reversible, pronounced membrane curvature change as a result of strong membrane insertion of the comb-like pseudopeptides. The pseudopeptides can enable efficient intracellular delivery of not only trehalose for improved cell cryopreservation, but also other membrane-impermeable cargos.
Issue Date: 1-Jul-2020
Date of Acceptance: 4-Jun-2020
URI: http://hdl.handle.net/10044/1/79930
DOI: 10.1021/acsami.0c03260
ISSN: 1944-8244
Publisher: American Chemical Society (ACS)
Start Page: 28941
End Page: 28951
Journal / Book Title: ACS Applied Materials & Interfaces
Volume: 12
Issue: 26
Copyright Statement: © 2020 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Materials and Interfaces, after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsami.0c03260
Sponsor/Funder: GlaxoSmithKline Services Unlimited
Funder's Grant Number: 3001437872/Richard Zajicek
Keywords: Science & Technology
Technology
Nanoscience & Nanotechnology
Materials Science, Multidisciplinary
Science & Technology - Other Topics
Materials Science
pH-responsive
pseudopeptide
comb-like polymer
cryopreservation
blood
trehalose
PH-RESPONSIVE POLYMERS
RED-BLOOD-CELLS
MEMBRANE CURVATURE
MAMMALIAN-CELLS
MECHANISM
DESICCATION
PROTEINS
CRYOSURVIVAL
SURVIVAL
STRESS
blood
comb-like polymer
cryopreservation
pH-responsive
pseudopeptide
trehalose
Nanoscience & Nanotechnology
03 Chemical Sciences
09 Engineering
Publication Status: Published
Article Number: acsami.0c03260
Online Publication Date: 2020-06-04
Appears in Collections:Chemical Engineering
Faculty of Engineering