RT Journal Article
T1 SiRNA silencing by chemically modified biopolymeric nanovectors
A1 Villar Álvarez, Eva María
A1 Leal, Baltazar H.
A1 Martínez González, Raquel
A1 Pardo Montero, Alberto
A1 Al-Qadi, Sonia
A1 Juárez, Josué
A1 Váldez, Miguel A.
A1 Cambón Freire, Adriana
A1 Barbosa Fernández, Silvia
A1 Taboada Antelo, Pablo
K1 Genetics
K1 Fluorescence
K1 Hydrophobicity
K1 Gene delivery
K1 Biopolymers
AB The ability to specifically silence genes by RNAinterference has an enormous potential for treating geneticdiseases. However, different drawbacks such as shortinterfering RNA (siRNA) degradability by serum nucleasesand biodistribution issues still need to be overcome to developsuitable delivery vehicles that have been proven essential incarrying siRNA to its target. Chitosan is an attractivebiomaterial to construct gene nanocarriers as it is safe,cheap, and amenable to chemical modifications. However, thetransfection efficiency of nanovectors based on unmodifiedchitosan has revealed to be relatively low and dependent on different factors such as the biopolymer molecular weight,deacetylation degree, charge ratio, pH, or particle size. Thus, specific strategies have been adopted to improve the transfectionefficacy of chitosan-based nanovectors. In this work, hydrophobically modified chitosans with 8-, 10-, and 12-carbon side chainsgrafted to the polymeric backbone by a reductive amination process were used to develop polymeric nanoparticles by theionotropic gelation method. After chitosan modification, the produced nanoparticles showed a suitable combination of size andsurface charge with high siRNA loading capacities, efficient protection against serum nucleases, and satisfactory in vitro releaseprofiles. Importantly, the introduced structural modifications were observed to modulate the overall physicochemicalcharacteristics of the nanoparticles including their biological performance like their cell viability, uptake, and transfectionefficiency. In this regard, the knockdown activity of the prepared nanoparticles was tested in HeLa cells overexpressing the greenfluorescent protein after 24 and 48 h of incubation, observing a silencing activity greater than that displayed by the commercialtransfection agent Lipofectamine 2000
PB American Chemical Society
YR 2019
FD 2019
LK http://hdl.handle.net/10347/21363
UL http://hdl.handle.net/10347/21363
LA eng
NO Villar-Alvarez, E., Leal, B., Martínez-González, R., Pardo, A., Al-Qadi, S., Juárez, J., Váldez, M., Cambón, A., Barbosa, S. and Taboada, P., 2019. siRNA Silencing by Chemically Modified Biopolymeric Nanovectors. ACS Omega, 4(2), 3904-3921
NO This work was supported by the Agencia Estatal deInvestigación (AEI) through Project MAT2016-80266-R andXunta de Galicia (Grupo de Referencia Competitiva ED431C2018/26; Agrupación Estratégica en Materiales-AEMATED431E 2018/08). FEDER funds are also acknowledged.A.C. also thanks Xunta de Galicia for her postdoctoralfellowship. E.V.-A. and A.P. are also grateful to the SpanishMinisterio de Economia y Competitividad for their FPUfellowships
DS Minerva
RD 27 abr 2026