Jump to main content
Jump to site search
PLANNED MAINTENANCE Close the message box

Scheduled maintenance work on Wednesday 21st October 2020 from 07:00 AM to 07:00 PM (BST).

During this time our website performance may be temporarily affected. We apologise for any inconvenience this might cause and thank you for your patience.


Issue 23, 2020
Previous Article Next Article

Tuning of endosomal escape and gene expression by functional groups, molecular weight and transfection medium: a structure–activity relationship study

Author affiliations

Abstract

The use of genetic material by non-viral transfer systems is still in its initial stages, but there are high expectations for the development of targeted therapies. However, nucleic acids cannot enter cells without help, they must be well protected to prevent degradation and overcome a variety of biological barriers, the endosomal barrier being one of the greatest cellular challenges. Herein, the structure–property-relationship was investigated in detail, using well-defined polymers. Polyacrylamides were synthesized via RAFT polymerization resulting in a polymer library of (i) different cationic groups as aminoethyl acrylamide (AEAm), dimethylaminoethyl acrylamide (DMAEAm), dimethylaminopropyl acrylamide (DMAPAm) and guanidinopropyl acrylamide (GPAm); (ii) different degree of polymerization; and investigated (iii) in different cell culture settings. The influence of molar mass and cationic moiety on complex formation with pDNA, cytotoxicity and transfection efficiency of the polymers were investigated. The systematic approach identified a pH-independent guanidinium-containing homopolymer (PGPAm89) as the polymer with the highest transfection efficiency and superior endosomal release under optimal conditions. Since PGPAm89 is not further protonated inside endosomes, common escape theories appear unsuitable. Therefore, the interaction with bis(monoacryloylglycerol)phosphate, a lipid specific for endosomal vesicles, was investigated. Our research suggests that the interactions between amines and lipids may be more relevant than anticipated.

Graphical abstract: Tuning of endosomal escape and gene expression by functional groups, molecular weight and transfection medium: a structure–activity relationship study

Back to tab navigation

Supplementary files

Article information


Submitted
07 Feb 2020
Accepted
06 Apr 2020
First published
08 Apr 2020

J. Mater. Chem. B, 2020,8, 5026-5041
Article type
Paper

Tuning of endosomal escape and gene expression by functional groups, molecular weight and transfection medium: a structure–activity relationship study

F. Richter, L. Martin, K. Leer, E. Moek, F. Hausig, J. C. Brendel and A. Traeger, J. Mater. Chem. B, 2020, 8, 5026
DOI: 10.1039/D0TB00340A

Social activity

Search articles by author

Spotlight

Advertisements