Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/43920
Registo completo
Campo DC | Valor | Idioma |
---|---|---|
dc.contributor.author | Oliveira, Ana Cristina Norberto Gonçalves | por |
dc.contributor.author | Sarria, Marisa Passos | por |
dc.contributor.author | Moreira, Pedro | por |
dc.contributor.author | Fernandes, Joana | por |
dc.contributor.author | Castro, Lisandra Marisa Flores | por |
dc.contributor.author | Lopes, Ivo | por |
dc.contributor.author | Côrte-Real, Manuela | por |
dc.contributor.author | Cavaco-Paulo, Artur | por |
dc.contributor.author | Real Oliveira, M. Elisabete C.D. | por |
dc.contributor.author | Gomes, Andreia C | por |
dc.date.accessioned | 2016-12-27T19:36:20Z | - |
dc.date.available | 2016-12-27T19:36:20Z | - |
dc.date.issued | 2016-06-13 | - |
dc.date.submitted | 2016-02-25 | - |
dc.identifier.citation | Oliveira, A. C. N., Sarria, M. P., Moreira, P., Fernandes, J., Castro, L., Lopes, I., . . . Gomes, A. C. (2016). Counter ions and constituents combination affect DODAX: MO nanocarriers toxicity in vitro and in vivo. Toxicology Research, 5(4), 1244-1255. doi: 10.1039/c6tx00074f | por |
dc.identifier.issn | 2045-452X | por |
dc.identifier.uri | https://hdl.handle.net/1822/43920 | - |
dc.description.abstract | Liposomes have received extensive attention as nanocarriers for bioactive compounds due to their good biocompatibility, possibility of targeting and incorporation of hydrophilic and hydrophobic compounds. Although generally considered as safe, detailed knowledge of the effects induced in cells and tissues with which they interact is still underexplored. The aim of this study is to gain insight into the toxicity profile of dioctadecyldimethylammonium (DODAX) : monoolein(MO) liposomes (X is bromide or chloride), previously validated for gene therapy, by evaluating the effect of the counter ions Br− or Cl−, and of the cationic : neutral lipid molar fraction, both in vitro and in vivo. Effects on cellular metabolism and proliferation, plasma membrane integrity, oxidative stress, mitochondrial membrane potential dysfunction and ability to trigger apoptosis and necrosis were evaluated in a dose-/time-dependent manner in normal human skin fibroblasts. Also, newly fertilized zebrafish zygotes were exposed to liposomes, permitting a fast-track evaluation of the morphophysiological modifications. In vitro data showed that only very high doses of DODAX : MO induce apoptosis and necrosis, inhibit cell proliferation, and affect the metabolism and plasma membrane integrity of fibroblasts in a dose-/time-dependent manner. Furthermore, liposomes affected mitochondrial function, increasing ROS accumulation and disturbing mitochondrial membrane potential. DODAC-based liposomes were consistently more toxic when compared to DODAB-based formulations; furthermore, the inclusion of MO was found to reduce toxicity, in contrast to liposomes with cationic DODAX only, especially in DODAB : MO (1 : 2) nanocarriers. These results were corroborated, in a holistic approach, by cytotoxicity profiling in five additional human cell lines, and also with the zebrafish embryotoxicity testing, which constitutes a sensitive and informative tool and accurately extends cell-based assays. | por |
dc.description.sponsorship | This work was supported by the strategic programme UID/BIA/ 04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI); by FEDER through POFCCOMPETE; and by national funds from FCT through PEstC/FIS/UI0607/2013 (CFUM) and PTDC/QUI/69795/2006. Ana Oliveira held the scholarship, SFRH/BD/68588/2010. Marisa P. Sárria holds a Marie Curie COFUND fellowship funding from the European Union’s7 th Framework Programme for research, technological development and demonstration under grant agreement 600375. The authors are grateful to the technical support of Marinnova – Marine and Environmental Innovation, Technology and Services, a R&I company anchored to the Centre of Marine and Environmental Research (CIIMAR – University of Porto, Portugal), focused at providing innovative services and products in the field of marine and environmental sciences. | por |
dc.language.iso | eng | por |
dc.publisher | Royal Society of Chemistry | por |
dc.relation | info:eu-repo/grantAgreement/FCT/5876/147364/PT | por |
dc.relation | info:eu-repo/grantAgreement/FCT/COMPETE/132974/PT | por |
dc.relation | info:eu-repo/grantAgreement/FCT/5876-PPCDTI/69795/PT | por |
dc.relation | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F68588%2F2010/PT | por |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/600375/EU | por |
dc.rights | openAccess | por |
dc.subject | Toxicology. zebra fish | por |
dc.title | Counter ions and constituents combination affect DODAX: MO nanocarriers toxicity in vitro and in vivo | por |
dc.type | article | por |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | http://pubs.rsc.org/en/Content/ArticleLanding/2016/TX/c6tx00074f#!divAbstract | por |
sdum.publicationstatus | info:eu-repo/semantics/publishedVersion | por |
oaire.citationStartPage | 1244 | por |
oaire.citationEndPage | 1255 | por |
oaire.citationIssue | 4 | por |
oaire.citationTitle | Toxicology Research | por |
oaire.citationVolume | 4 | por |
dc.identifier.doi | 10.1039/C6TX00074F | por |
dc.subject.fos | Ciências Médicas::Outras Ciências Médicas | por |
dc.subject.wos | Science & Technology | por |
sdum.journal | Toxicology Research | por |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series CBMA - Artigos/Papers CDF - FAMO - Artigos/Papers (with refereeing) DBio - Artigos/Papers |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
---|---|---|---|---|
Oliveira et al. Toxicology Research 2016.pdf | 1,77 MB | Adobe PDF | Ver/Abrir |