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doi:10.22028/D291-43349
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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