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Molecular determinants for cyclo-oligosaccharide-based nanoparticle-mediated effective siRNA transfection

AuthorsManzarares, Darío; Araya-Durán, Ingrid; Gallego-Yerga, Laura; Játiva, Pablo; Márquez-Miranda, Valeria; Canan, Jonathan; Jiménez Blanco, José Luis; Ortiz Mellet, Carmen; González-Nilo, Fernando Danilo; García Fernández, José Manuel ; Ceña, Valentín
KeywordsProtection from RNAses
Molecular nanoparticle
Protein knock down
siRNA transfection
Molecular modeling
Endosomal escape
Issue Date16-Jun-2017
PublisherFuture Medicine
CitationNanomedicine 12(13): 1607-1621 (2017)
Abstract[Aim] To study the structural requirements that a cyclooligosaccharide-based nanoparticle must fulfill to be an efficient siRNA transfection vector.[Materials & methods] siRNA protection from degradation by RNAses, transfection efficiency and the thermodynamic parameters of the nanoparticle/siRNA interactions were studied on pairs of amphiphilic molecules using biochemical techniques and molecular dynamics.
[Results] The lower the siRNA solvent accessible surface area in the presence of the nanoparticle, higher the protection from RNAse-mediated degradation in the corresponding nanocomplex; a moderate nanoparticle/siRNA binding energy value further facilitates reversible complexation and binding to the target cellular mRNA.
[Conclusion] The use, in advance, of these parameters will provide a useful indication of the potential of a molecular nanoparticle as siRNA transfecting vector.
Publisher version (URL)https://doi.org/10.2217/nnm-2017-0123
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