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Characterization and comparison of two novel nanosystems associated with siRNA for cellular therapy

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dc.contributor.authorAndré, E. M.
dc.contributor.authorPensado, A.
dc.contributor.authorResnier, P.
dc.contributor.authorBraz, L.
dc.contributor.authorCosta, Ana M. Rosa da
dc.contributor.authorPassirani, C.
dc.contributor.authorSanchez, A.
dc.contributor.authorMontero-Menei, C. N.
dc.date.accessioned2016-01-06T17:36:32Z
dc.date.available2016-01-06T17:36:32Z
dc.date.issued2016
dc.description.abstractTo direct stem cell fate, a delicate control of gene expression through small interference RNA (siRNA) is emerging as a new and safe promising strategy. In this way, the expression of proteins hindering neuronal commitment may be transiently inhibited thus driving differentiation. Mesenchymal stem cells (MSC), which secrete tissue repair factors, possess immunomodulatory properties and may differentiate towards the neuronal lineage, are a promising cell source for cell therapy studies in the central nervous system. To better drive their neuronal commitment the repressor Element-1 silencing transcription (REST) factor, may be inhibited by siRNA technology. The design of novel nanoparticles (NP) capable of safely delivering nucleic acids is crucial in order to successfully develop this strategy. In this study we developed and characterized two different siRNA NP. On one hand, sorbitan monooleate (Span(®)80) based NP incorporating the cationic components poly-l-arginine or cationized pullulan, thus allowing the association of siRNA were designed. These NP presented a small size (205nm) and a negative surface charge (-38mV). On the other hand, lipid nanocapsules (LNC) associating polymers with lipids and allowing encapsulation of siRNA complexed with lipoplexes were also developed. Their size was of 82nm with a positive surface charge of +7mV. Both NP could be frozen with appropriate cryoprotectors. Cytotoxicity and transfection efficiency at different siRNA doses were monitored by evaluating REST expression. An inhibition of around 60% of REST expression was observed with both NP when associating 250ng/mL of siRNA-REST, as recommended for commercial reagents. Span NP were less toxic for human MSCs than LNCs, but although both NP showed a similar inhibition of REST over time and the induction of neuronal commitment, LNC-siREST induced a higher expression of neuronal markers. Therefore, two different tailored siRNA NP offering great potential for human stem cell differentiation have been developed, encouraging the pursuit of further in vitro and in vivo in studies.pt_PT
dc.description.sponsorshipGrants of the Ministry of Economy and Competitiveness of Spain (MAT2013-47501-C2-2-R); Xunta de Galicia (Competitive Reference Groups, FEDER Funds, Ref. 2014/043)
dc.identifier.citationInternational Journal of Pharmaceutics 497 (2016) 255–267pt_PT
dc.identifier.doihttp:/dx.doi.org/10.1016/j.ijpharm.2015.11.020pt_PT
dc.identifier.issn0378-5173
dc.identifier.otherAUT: AMC01695;
dc.identifier.urihttp://hdl.handle.net/10400.1/7392
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationStrategic Project - UI 4023 - 2011-2012
dc.relation.publisherversionhttp://ac.els-cdn.com/S0378517315303677/1-s2.0-S0378517315303677-main.pdf?_tid=c8f9e68c-a8bc-11e5-83c8-00000aacb35d&acdnat=1450796628_d6e2e72284b7e66ec0ba53aa061190eept_PT
dc.subjectNanocarrierspt_PT
dc.subjectsiRNApt_PT
dc.subjectMesenchymal stem cellspt_PT
dc.subjectNeuronal differentiationpt_PT
dc.subjectRESTpt_PT
dc.titleCharacterization and comparison of two novel nanosystems associated with siRNA for cellular therapypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleStrategic Project - UI 4023 - 2011-2012
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FQUI%2FUI4023%2F2011/PT
oaire.citation.endPage267pt_PT
oaire.citation.issue1-2pt_PT
oaire.citation.startPage255pt_PT
oaire.citation.titleInternational Journal of Pharmaceuticspt_PT
oaire.citation.volume497pt_PT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameBraz
person.familyNameRosa da Costa
person.givenNameLuis
person.givenNameAna M
person.identifier305029
person.identifier.ciencia-idBA15-0A43-361F
person.identifier.ciencia-idA418-A85E-5DB1
person.identifier.orcid0000-0002-1500-1976
person.identifier.orcid0000-0003-0225-9537
person.identifier.ridE-1901-2012
person.identifier.ridE-2165-2012
person.identifier.scopus-author-id55996112700
person.identifier.scopus-author-id53986075100
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication33ff57b7-7297-41b0-9cdb-acc1cac47463
relation.isAuthorOfPublication0ca8c16f-6881-4662-bafc-cc51c5ce8d88
relation.isAuthorOfPublication.latestForDiscovery0ca8c16f-6881-4662-bafc-cc51c5ce8d88
relation.isProjectOfPublicationb1adbc46-7371-4ed4-a74e-a181b403ca4d
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