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Richter, Friederike ; Martin, Liam ; Leer, Katharina ; Moek, Elisabeth ; Hausig, Franziska ; Brendel, Johannes C. ; Traeger, Anja:
Tuning of endosomal escape and gene expression by functional groups, molecular weight and transfection medium : a structure–activity relationship study.
In: Journal of Materials Chemistry B.
Bd. 8
(2020)
Heft 23
.
- S. 5026-5041.
ISSN 2050-7518
DOI: https://doi.org/10.1039/D0TB00340A
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.
Weitere Angaben
| Publikationsform: | Artikel in einer Zeitschrift |
|---|---|
| Begutachteter Beitrag: | Ja |
| Institutionen der Universität: | Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Lehrstuhl Makromolekulare Chemie I |
| Titel an der UBT entstanden: | Nein |
| Themengebiete aus DDC: | 500 Naturwissenschaften und Mathematik > 540 Chemie |
| Eingestellt am: | 19 Feb 2024 14:14 |
| Letzte Änderung: | 19 Feb 2024 14:14 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/88614 |