Please use this identifier to cite or link to this item: doi:10.22028/D291-38735
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Title: Proteoid biodynamers for safe mRNA transfection via pH-responsive nanorods enabling endosomal escape
Author(s): Lee, Sangeun
Nasr, Sarah Samir Mahmoud
Rasheed, Sari Shawki
Liu, Yun
Hartwig, Olga
Kaya, Cansu
Boese, Annette
Koch, Marcus
Herrmann, Jennifer
Müller, Rolf
Loretz, Brigitta
Buhler, Eric
Hirsch, Anna
Lehr, Claus-Michael
Language: English
Title: Journal of controlled release : official journal of the Controlled Release Society
Volume: 353
Pages: 915-929
Publisher/Platform: Elsevier
Year of Publication: 2023
DDC notations: 500 Science
Publikation type: Journal Article
Abstract: The recent success of mRNA vaccines using lipid-based vectors highlights the importance of strategies for nucleotide delivery under the pandemic situation. Although current mRNA delivery is focused on lipid-based vectors, still they need to be optimized for increasing stability, targeting, and efficiency, and for reducing toxicity. In this regard, other vector systems featuring smart strategies such as pH-responsive degradability and endosomal escape ability hold the potential to overcome the current limitations. Here, we report pH-responsive polymeric nanorods made of amino acid-derivatives connected by dynamic covalent bonds called proteoid-biodynamers, as mRNA vectors. They show excellent biocompatibility due to the biodegradation, and outstanding transfection. The biodynamers of Lys, His, and Arg or monomer mixtures thereof were shown to form nanocomplexes with mRNA. They outperformed conventional transfection agents three times regarding transfection efficacy in three human cell lines, with 82-98% transfection in living cells. Also, we confirmed that the biodynamers disrupted the endosomes up to 10-fold more in number than the conventional vectors. We discuss here their outstanding performance with a thorough analysis of their nanorod structure changes in endosomal microenvironments.
DOI of the first publication: 10.1016/j.jconrel.2022.12.018
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-387350
ISSN: 0168-3659
Date of registration: 20-Jan-2023
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Chemie
NT - Pharmazie
Professorship: NT - Prof. Dr. Anna Hirsch
NT - Prof. Dr. Claus-Michael Lehr
NT - Prof. Dr. Rolf Müller
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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