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Titel: pH-Responsive Dynaplexes as Potent Apoptosis Inductors by Intracellular Delivery of Survivin siRNA
VerfasserIn: Liu, Yun
Ashmawy, Salma
Latta, Lorenz
Weiss, Agnes-Valencia
Kiefer, Alexander F.
Nasr, Sarah
Loretz, Brigitta
Hirsch, Anna K. H.
Lee, Sangeun
Lehr, Claus-Michael
Sprache: Englisch
Titel: Biomacromolecules
Bandnummer: 24
Heft: 8
Verlag/Plattform: ACS
Erscheinungsjahr: 2023
Freie Schlagwörter: Apoptosis
Gene Delivery
Genetics
Monomers
Nucleic Acid Structure
DDC-Sachgruppe: 500 Naturwissenschaften
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Gene knockdown by siRNA offers an unrestricted choice of targets and specificity based on the principle of complementary Watson−Crick base pairing with mRNA. However, the negative charge, large molecular size, and susceptibility to enzymatic degradation of siRNA impede its successful transfection, hence limiting its potential for therapeutic use. The development of efficient and safe siRNA transfection agents is, therefore, critical for siRNA-based therapy. Herein, we developed a protein-based biodynamic polymer (biodynamer) that showed potential as a siRNA transfection vector, owing to its excellent biocompatibility, easy tunability, and dynamic polymerization under acidic environments. The positively charged biodynamers formed stable dynamic nanocomplexes (XL-DPs, hydrodynamic diameter of approximately 104 nm) with siRNA via electrostatic interactions and chemical cross-linking. As a proof of concept, the optimized XL-DPs were stable in physiological conditions with serum proteins and demonstrated significant pH-dependent size change and degradability, as well as siRNA release capability. The minimal cytotoxicity and excellent cellular uptake of XL-DPs effectively supported the intracellular delivery of siRNA. Our study demonstrated that the XL-DPs in survivin siRNA delivery enabled potent knockdown of survivin mRNA and induced notable apoptosis of carcinoma cells (2.2 times higher than a lipid-based transfection agent, Lipofectamine 2000). These findings suggested that our XL-DPs hold immense potential as a promising platform for siRNA delivery and can be considered strong candidates in the advancement of next-generation transfection agents.
DOI der Erstveröffentlichung: 10.1021/acs.biomac.3c00424
URL der Erstveröffentlichung: https://pubs.acs.org/doi/10.1021/acs.biomac.3c00424
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-433499
hdl:20.500.11880/38880
http://dx.doi.org/10.22028/D291-43349
ISSN: 1526-4602
1525-7797
Datum des Eintrags: 5-Nov-2024
Bezeichnung des in Beziehung stehenden Objekts: Supporting information
In Beziehung stehendes Objekt: https://ndownloader.figstatic.com/files/41776772
Fakultät: NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: NT - Pharmazie
Professur: NT - Prof. Dr. Anna Hirsch
NT - Prof. Dr. Claus-Michael Lehr
NT - Prof. Dr. Marc Schneider
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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