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A versatile polymer‐based platform for intracellular delivery of macromolecules

Title: A versatile polymer‐based platform for intracellular delivery of macromolecules
Authors: Kopytynski, M
Chen, S
Legg, S
Minter, R
Chen, R
Item Type: Journal Article
Abstract: The plasma membrane barrier greatly restricts intracellular delivery of macromolecules. Currently available methods suffer from various limitations, including low delivery efficiency, high cytotoxicity or incompatibility with a wider range of macromolecules or cell types. To overcome these issues, stimuli-responsive polymers such as the bio-inspired, pH-responsive poly(L-lysine isophthalamide) grafted with L-phenylalanine at a stoichiometric ratio of 50% (PP50) can be used. In mildly acidic environments, the pseudopeptidic polymer can permeabilize the plasma membrane overcoming the problem of payload entrapment in the endosomes and allowing for efficient intracellular delivery. We demonstrate that PP50 was capable of intracellular delivery by simple co-incubation at pH 6.5 with various macromolecules, including different-sized Dextrans, green fluorescent protein (GFP) and an apoptotic peptide. The delivery process was fast, non-toxic and compatible with multiple cell types, including adherent and suspension cell lines, primary human mesenchymal stem cells, and cells grown as spheroids. In addition, apoptotic peptide delivery by co-incubation with PP50 was over 3 times more effective than delivery using other common methods, including poly(ethyleneimine) (PEI), cell penetrating peptides (CPPs) and electroporation. Our findings suggest that payload delivery by co-incubation with PP50 is a flexible, controllable method allowing delivery of various payloads to many different cell types in vitro.
Date of Acceptance: 3-Nov-2019
URI: http://hdl.handle.net/10044/1/75699
DOI: 10.1002/adtp.201900169
ISSN: 2366-3987
Publisher: Wiley
Start Page: 1
End Page: 10
Journal / Book Title: Advanced Therapeutics
Volume: 3
Issue: 2
Copyright Statement: © 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is the accepted version of the following article: Kopytynski, M., Chen, S., Legg, S., Minter, R. and Chen, R. (2019), A Versatile Polymer‐Based Platform for Intracellular Delivery of Macromolecules. Adv. Therap, which has been published in final form at https://doi.org/10.1002/adtp.201900169
Sponsor/Funder: GlaxoSmithKline Services Unlimited
Biotechnology and Biological Sciences Research Council
MedImmune
Funder's Grant Number: Mark Buswell
BB/L016044/1
Ralph Minter
Keywords: Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
apoptotic peptide
drug delivery
macromolecular delivery
pH-responsive polymer
spheroids
PH-RESPONSIVE POLYMERS
CELL-PENETRATING PEPTIDES
DRUG-DELIVERY
GENE DELIVERY
IN-VITRO
LIVE CELLS
PROTEINS
MECHANISMS
BIOPOLYMER
STRATEGIES
apoptotic peptide
drug delivery
macromolecular delivery
pH-responsive polymer
spheroids
Publication Status: Published online
Online Publication Date: 2019-12-12
Appears in Collections:Chemical Engineering
Faculty of Engineering