Journal
MOLECULAR SYSTEMS DESIGN & ENGINEERING
Volume 3, Issue 4, Pages 677-689Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c8me00006a
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Funding
- Grup d'Enginyeria dels Materials (GEMAT)
- Agencia de Gestio d'Ajuts Universitaris i de Recerca, Generalitat de Catalunya (SGR 2014) [1170]
- AGAUR (Generalitat de Catalunya) [2017FI_B2 00141]
- Spanish Ministerio de Economia y Competitividad (MINECO) [SAF2015-64927-C2-2-R]
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Cationic polymers are promising delivery systems for RNAi due to their ease of manipulation, scale-up conditions and transfection efficiency. However, some properties, such as stability and targeting, remain challenging to overcome. In this report, different modifications in poly(-amino ester) (pBAE) structures have been explored to overcome these limitations. Recent studies have demonstrated that hydrophobicity plays a key role in controlling electrostatic interactions of plasma proteins with nanoparticles. Results show that a slight increase in the polymer hydrophobicity increases its siRNA packaging capacity, stability, and transfection efficiency. Consequently, polyplexes prepared with these hydrophobic structures are functional after incubation times longer than 48 hours in serum-containing medium. In addition, newly designed polymers were end-modified using different oligopeptide moieties in order to confer cell-specificity, as previously reported. Therefore, it can be concluded that these newly optimized pBAE polymers present great potential as delivery vectors to specifically drive therapeutic RNA-based nucleic acids in a cell-specific manner under physiological conditions.
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