Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems
Co-delivery of different species of protein-encoding polynucleotides, e.g., messenger RNA (mRNA) and plasmid DNA (pDNA), using the same nanocarrier is an interesting topic that remains scarcely researched in the field of nucleic acid delivery. The current study hence aims to explore the possibility...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/11/1924 |
| _version_ | 1797508794924662784 |
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| author | Sarah S. Nasr Sangeun Lee Durairaj Thiyagarajan Annette Boese Brigitta Loretz Claus-Michael Lehr |
| author_facet | Sarah S. Nasr Sangeun Lee Durairaj Thiyagarajan Annette Boese Brigitta Loretz Claus-Michael Lehr |
| author_sort | Sarah S. Nasr |
| collection | DOAJ |
| description | Co-delivery of different species of protein-encoding polynucleotides, e.g., messenger RNA (mRNA) and plasmid DNA (pDNA), using the same nanocarrier is an interesting topic that remains scarcely researched in the field of nucleic acid delivery. The current study hence aims to explore the possibility of the simultaneous delivery of mRNA (mCherry) and pDNA (pAmCyan) using a single nanocarrier. The latter is based on gelatin type A, a biocompatible, and biodegradable biopolymer of broad pharmaceutical application. A core-shell nanostructure is designed with a thermally stabilized gelatin–pDNA coacervate in its center. Thermal stabilization enhances the core’s colloidal stability and pDNA shielding effect against nucleases as confirmed by nanoparticle tracking analysis and gel electrophoresis, respectively. The stabilized, pDNA-loaded core is coated with the cationic peptide protamine sulfate to enable additional surface-loading with mRNA. The dual-loaded core-shell system transfects murine dendritic cell line DC2.4 with both fluorescent reporter mRNA and pDNA simultaneously, showing a transfection efficiency of 61.4 ± 21.6% for mRNA and 37.6 ± 19.45% for pDNA, 48 h post-treatment, whereas established commercial, experimental, and clinical transfection reagents fail. Hence, the unique co-transfectional capacity and the negligible cytotoxicity of the reported system may hold prospects for vaccination among other downstream applications. |
| first_indexed | 2024-03-10T05:08:57Z |
| format | Article |
| id | doaj.art-64843125f8e34c3baf987154636b6717 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T05:08:57Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-64843125f8e34c3baf987154636b67172023-11-23T00:59:44ZengMDPI AGPharmaceutics1999-49232021-11-011311192410.3390/pharmaceutics13111924Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell NanosystemsSarah S. Nasr0Sangeun Lee1Durairaj Thiyagarajan2Annette Boese3Brigitta Loretz4Claus-Michael Lehr5Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123 Saarbrücken, GermanyHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123 Saarbrücken, GermanyHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123 Saarbrücken, GermanyHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123 Saarbrücken, GermanyHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123 Saarbrücken, GermanyHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123 Saarbrücken, GermanyCo-delivery of different species of protein-encoding polynucleotides, e.g., messenger RNA (mRNA) and plasmid DNA (pDNA), using the same nanocarrier is an interesting topic that remains scarcely researched in the field of nucleic acid delivery. The current study hence aims to explore the possibility of the simultaneous delivery of mRNA (mCherry) and pDNA (pAmCyan) using a single nanocarrier. The latter is based on gelatin type A, a biocompatible, and biodegradable biopolymer of broad pharmaceutical application. A core-shell nanostructure is designed with a thermally stabilized gelatin–pDNA coacervate in its center. Thermal stabilization enhances the core’s colloidal stability and pDNA shielding effect against nucleases as confirmed by nanoparticle tracking analysis and gel electrophoresis, respectively. The stabilized, pDNA-loaded core is coated with the cationic peptide protamine sulfate to enable additional surface-loading with mRNA. The dual-loaded core-shell system transfects murine dendritic cell line DC2.4 with both fluorescent reporter mRNA and pDNA simultaneously, showing a transfection efficiency of 61.4 ± 21.6% for mRNA and 37.6 ± 19.45% for pDNA, 48 h post-treatment, whereas established commercial, experimental, and clinical transfection reagents fail. Hence, the unique co-transfectional capacity and the negligible cytotoxicity of the reported system may hold prospects for vaccination among other downstream applications.https://www.mdpi.com/1999-4923/13/11/1924nucleic acid vaccinecomplex coacervationnanocarriersanisotropic nanogelphysical cross-linkingdual loading |
| spellingShingle | Sarah S. Nasr Sangeun Lee Durairaj Thiyagarajan Annette Boese Brigitta Loretz Claus-Michael Lehr Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems Pharmaceutics nucleic acid vaccine complex coacervation nanocarriers anisotropic nanogel physical cross-linking dual loading |
| title | Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems |
| title_full | Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems |
| title_fullStr | Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems |
| title_full_unstemmed | Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems |
| title_short | Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems |
| title_sort | co delivery of mrna and pdna using thermally stabilized coacervate based core shell nanosystems |
| topic | nucleic acid vaccine complex coacervation nanocarriers anisotropic nanogel physical cross-linking dual loading |
| url | https://www.mdpi.com/1999-4923/13/11/1924 |
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