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Synthesis and application of spermine-based amphiphilic poly(β-amino ester)s for siRNA delivery
Small interfering RNA (siRNA) can trigger RNA interference (RNAi) to therapeutically silence disease-related genes in human cells. The approval of siRNA therapeutics by the FDA in recent years generated a new hope in novel and efficient siRNA therapeutics. However, their therapeutic application is s...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
RSC
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521211/ https://www.ncbi.nlm.nih.gov/pubmed/37767040 http://dx.doi.org/10.1039/d3na00272a |
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author | Jin, Yao Adams, Friederike Nguyen, Anny Sturm, Sebastian Carnerio, Simone Müller-Caspary, Knut Merkel, Olivia M. |
author_facet | Jin, Yao Adams, Friederike Nguyen, Anny Sturm, Sebastian Carnerio, Simone Müller-Caspary, Knut Merkel, Olivia M. |
author_sort | Jin, Yao |
collection | PubMed |
description | Small interfering RNA (siRNA) can trigger RNA interference (RNAi) to therapeutically silence disease-related genes in human cells. The approval of siRNA therapeutics by the FDA in recent years generated a new hope in novel and efficient siRNA therapeutics. However, their therapeutic application is still limited by the lack of safe and efficient transfection vehicles. In this study, we successfully synthesized a novel amphiphilic poly(β-amino ester) based on the polyamine spermine, hydrophobic decylamine and 1,4-butanediol diacrylate, which was characterized by (1)H NMR spectroscopy and size exclusion chromatography (SEC, M(n) = 6000 Da). The polymer encapsulated siRNA quantitatively from N/P 5 on as assessed by fluorescence intercalation while maintaining optimal polyplex sizes and zeta potentials. Biocompatibility and cellular delivery efficacy were also higher than those of the commonly used cationic, hyperbranched polymer polyethylenimine (PEI, 25 kDa). Optimized formulations mediated around 90% gene silencing in enhanced green fluorescence protein expressing H1299 cells (H1299-eGFP) as determined by flow cytometry. These results suggest that spermine-based, amphiphilic poly(β-amino ester)s are very promising candidates for efficient siRNA delivery. |
format | Online Article Text |
id | pubmed-10521211 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | RSC |
record_format | MEDLINE/PubMed |
spelling | pubmed-105212112023-09-27 Synthesis and application of spermine-based amphiphilic poly(β-amino ester)s for siRNA delivery Jin, Yao Adams, Friederike Nguyen, Anny Sturm, Sebastian Carnerio, Simone Müller-Caspary, Knut Merkel, Olivia M. Nanoscale Adv Chemistry Small interfering RNA (siRNA) can trigger RNA interference (RNAi) to therapeutically silence disease-related genes in human cells. The approval of siRNA therapeutics by the FDA in recent years generated a new hope in novel and efficient siRNA therapeutics. However, their therapeutic application is still limited by the lack of safe and efficient transfection vehicles. In this study, we successfully synthesized a novel amphiphilic poly(β-amino ester) based on the polyamine spermine, hydrophobic decylamine and 1,4-butanediol diacrylate, which was characterized by (1)H NMR spectroscopy and size exclusion chromatography (SEC, M(n) = 6000 Da). The polymer encapsulated siRNA quantitatively from N/P 5 on as assessed by fluorescence intercalation while maintaining optimal polyplex sizes and zeta potentials. Biocompatibility and cellular delivery efficacy were also higher than those of the commonly used cationic, hyperbranched polymer polyethylenimine (PEI, 25 kDa). Optimized formulations mediated around 90% gene silencing in enhanced green fluorescence protein expressing H1299 cells (H1299-eGFP) as determined by flow cytometry. These results suggest that spermine-based, amphiphilic poly(β-amino ester)s are very promising candidates for efficient siRNA delivery. RSC 2023-09-07 /pmc/articles/PMC10521211/ /pubmed/37767040 http://dx.doi.org/10.1039/d3na00272a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Jin, Yao Adams, Friederike Nguyen, Anny Sturm, Sebastian Carnerio, Simone Müller-Caspary, Knut Merkel, Olivia M. Synthesis and application of spermine-based amphiphilic poly(β-amino ester)s for siRNA delivery |
title | Synthesis and application of spermine-based amphiphilic poly(β-amino ester)s for siRNA delivery |
title_full | Synthesis and application of spermine-based amphiphilic poly(β-amino ester)s for siRNA delivery |
title_fullStr | Synthesis and application of spermine-based amphiphilic poly(β-amino ester)s for siRNA delivery |
title_full_unstemmed | Synthesis and application of spermine-based amphiphilic poly(β-amino ester)s for siRNA delivery |
title_short | Synthesis and application of spermine-based amphiphilic poly(β-amino ester)s for siRNA delivery |
title_sort | synthesis and application of spermine-based amphiphilic poly(β-amino ester)s for sirna delivery |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521211/ https://www.ncbi.nlm.nih.gov/pubmed/37767040 http://dx.doi.org/10.1039/d3na00272a |
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