Peptide nucleic acid-zirconium coordination nanoparticles
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Ideal 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 β -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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 14222 |
| Tidsskrift | Scientific Reports |
| Vol/bind | 13 |
| Antal sider | 16 |
| ISSN | 2045-2322 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
Open access funding provided by University of Vienna. E.W. acknowledges support by the German Research Foundation (DFG) SFB1032 (project-ID 201269156) sub-project B4. Ö.Ö. appreciate the YLSY fellowships granted by Turkish Ministry of Education as support to his Ph.D. study at Ludwig-Maximilians-Universität 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 Göl Öztürk 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.
Funding Information:
Open access funding provided by University of Vienna. E.W. acknowledges support by the German Research Foundation (DFG) SFB1032 (project-ID 201269156) sub-project B4. Ö.Ö. appreciate the YLSY fellowships granted by Turkish Ministry of Education as support to his Ph.D. study at Ludwig-Maximilians-Universität 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 Göl Öztürk 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. were created with Biorender.com.
Publisher Copyright:
© 2023, Springer Nature Limited.
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