Peptide nucleic acid-zirconium coordination nanoparticles

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dc.authorid0000-0001-8413-0934
dc.authorid0000-0002-4996-7592
dc.contributor.authorOzturk, Ozgur
dc.contributor.authorLessl, Anna-Lina
dc.contributor.authorHoehn, Miriam
dc.contributor.authorWuttke, Stefan
dc.contributor.authorNielsen, Peter E.
dc.contributor.authorWagner, Ernst
dc.contributor.authorLaechelt, Ulrich
dc.date.accessioned2026-01-24T12:31:21Z
dc.date.available2026-01-24T12:31:21Z
dc.date.issued2023
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractIdeal drug carriers feature a high loading capacity to minimize the exposure of patients with excessive, inactive carrier materials. The highest imaginable loading capacity could be achieved by nanocarriers, which are assembled from the therapeutic cargo molecules themselves. Here, we describe peptide nucleic acid (PNA)-based zirconium (Zr) coordination nanoparticles which exhibit very high PNA loading of > 94% w/w. This metal-organic hybrid nanomaterial class extends the enormous compound space of coordination polymers towards bioactive oligonucleotide linkers. The architecture of single-or double-stranded PNAs was systematically varied to identify design criteria for the coordination driven self-assembly with Zr(IV) nodes at room temperature. Aromatic carboxylic acid functions, serving as Lewis bases, and a two-step synthesis process with preformation of Zr6O4(OH)(4) turned out to be decisive for successful nanoparticle assembly. Confocal laser scanning microscopy confirmed that the PNA-Zr nanoparticles are readily internalized by cells. PNA-Zr nanoparticles, coated with a cationic lipopeptide, successfully delivered an antisense PNA sequence for splicing correction of the beta-globin intron mutation IVS2-705 into a functional reporter cell line and mediated splice-switching via interaction with the endogenous mRNA splicing machinery. The presented PNA-Zr nanoparticles represent a bioactive platform with high design flexibility and extraordinary PNA loading capacity, where the nucleic acid constitutes an integral part of the material, instead of being loaded into passive delivery systems.
dc.description.sponsorshipUniversity of Vienna; German Research Foundation (DFG) [201269156]; Turkish Ministry of Education; Galenus Foundation (Vienna, Austria)
dc.description.sponsorshipOpen access funding provided by University of Vienna. E.W. acknowledges support by the German Research Foundation (DFG) SFB1032 (project-ID 201269156) sub-project B4. OE.OE. appreciate the YLSY fellowships granted by Turkish Ministry of Education as support to his Ph.D. study at Ludwig-Maximilians-Universitaet Munich. U.L. appreciates support by the Galenus Foundation (Vienna, Austria). We thank Teoman Benli-Hoppe, Simone Berger and Tobias Burghardt for performing MALDI-TOF mass spectrometry measurements, Surhan Goel OEztuerk for help with cell cultures, Steffen Schmidt for SEM measurements, Shizhe Wang for XRD measurements and Faqian Shen for FT-IR measurements. The TOC-Figure, Scheme 1 and graphical elements in Fig. 4 were created with Biorender.com.
dc.identifier.doi10.1038/s41598-023-40916-w
dc.identifier.issn2045-2322
dc.identifier.issue1
dc.identifier.pmid37648689
dc.identifier.scopus2-s2.0-85169229974
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1038/s41598-023-40916-w
dc.identifier.urihttps://hdl.handle.net/20.500.12868/5826
dc.identifier.volume13
dc.identifier.wosWOS:001059012700032
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherNature Portfolio
dc.relation.ispartofScientific Reports
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20260121
dc.subjectMetal-Organic Frameworks
dc.subjectAntisense Activity
dc.subjectCellular Delivery
dc.subjectCationic Lipids
dc.subjectGene-Expression
dc.subjectDrug-Delivery
dc.subjectPna
dc.subjectDna
dc.subjectDesign
dc.subjectPolymers
dc.titlePeptide nucleic acid-zirconium coordination nanoparticles
dc.typeArticle

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