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Surface-PASylation of ferritin to form stealth nanovehicles enhances in vivo therapeutic performance of encapsulated ellipticine

2019-11-04Journal article Open access
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dc.contributor.authorTesarova, Barbora
dc.contributor.authorDostalova, Simona
dc.contributor.authorSmidova, Veronika
dc.contributor.authorGoliasova, Zita
dc.contributor.authorSkubalova, Zuzana
dc.contributor.authorMichalkova, Hana
dc.contributor.authorHynek, David
dc.contributor.authorMichalek, Petr
dc.contributor.authorPolanska, Hana
dc.contributor.authorVaculovicova, Marketa
dc.contributor.authorHacek, Jaromir
dc.contributor.authorEckschlager, Tomas
dc.contributor.authorStiborova, Marie
dc.contributor.authorPires, Ana S.
dc.contributor.authorNeves, Ana R.M.
dc.contributor.authorAbrantes, Ana M
dc.contributor.authorRodrigues, Tiago
dc.contributor.authorMatafome, Paulo
dc.contributor.authorBotelho, Maria F.
dc.contributor.authorTeixeira, Paulo
dc.contributor.authorMendes, Fernando 1973 -
dc.contributor.authorHeger, Zbynek
dc.date.accessioned2020-04-17T21:58:31Z
dc.date.available2020-04-17T21:58:31Z
dc.date.issued2019-11-04
dc.description.abstractSurface functionalisations substantially influence the performance of drug delivery vehicles by improving their biocompatibility, selectivity and circulation in bloodstream. Herein, we present the study of in vitro and in vivo behaviour of a highly potent cytostatic alkaloid ellipticine (Elli) encapsulated in internal cavity of ferritin (FRT)-based nanocarrier (hereinafter referred to as FRTElli). In addition, FRTElli surface was functionalised with three different molecular coatings: two types of protective PAS peptides (10- or 20-residues lengths) with sequences comprising amino acids proline (P), alanine (A) and serine (S) (to form PAS-10-FRTElli or PAS-20-FRTElli, respectively), or polyethylene glycol (PEG-FRTElli). All three surface modifications of FRT disposed sufficient encapsulation efficiency of Elli with no premature cumulative release of cargo. Noteworthy, all tested surface modifications displayed beneficial effects on the in vitro biocompatibility. PAS-10-FRTElli exhibited markedly reduced uptake by macrophages compared to PAS-20-FRTElli, PEG-FRTElli or unmodified FRTElli. The exceptional properties of PAS-10-FRTElli were validated by an array of in vitro analyses including formation of protein corona, uptake efficiency or screenings of selectivity of cytotoxicity. In murine preclinical model bearing triple-negative breast cancer (MDA-MB-231) xenograft, compared to free Elli or FRTElli, PAS-10-FRTElli displayed enhanced accumulation of Elli within tumour tissue, while hampering the uptake of Elli into off-target tissues. Noteworthy, PAS-10-FRTElli led to decreased in vivo complement (C3) activation and protein corona formation. Taken together, presented in vivo results indicate that PAS-10-FRTElli represents a promising stealth platform for translation into clinical settings.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citation2 B. Tesarova, S. Dostalova, V. Smidova et al. / Applied Materials Today 18 (2020) 100501pt_PT
dc.identifier.doi10.1016/j.apmt.2019.100501pt_PT
dc.identifier.issn2352-9415
dc.identifier.urihttp://hdl.handle.net/10400.26/32017
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/pt_PT
dc.subjectBiocompatibilitypt_PT
dc.subjectBreast carcinomapt_PT
dc.subjectCancer therapypt_PT
dc.subjectFerritinpt_PT
dc.subjectPasylationpt_PT
dc.subjectPegylationpt_PT
dc.titleSurface-PASylation of ferritin to form stealth nanovehicles enhances in vivo therapeutic performance of encapsulated ellipticinept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPage100501pt_PT
oaire.citation.titleApplied Materials Todaypt_PT
oaire.citation.volume18pt_PT
person.familyNameTesarova
person.familyNameDostalova
person.familyNameHynek
person.familyNameVaculovicova
person.familyNameEckschlager
person.familyNameStiborova
person.familyNameAbrantes
person.familyNameRodrigues
person.familyNameCenteio Matafome
person.familyNameTeixeira
person.familyNameHeger
person.givenNameBarbora
person.givenNameSimona
person.givenNameDavid
person.givenNameMarketa
person.givenNameTomas
person.givenNameMarie
person.givenNameAna M
person.givenNameTiago
person.givenNamePaulo Nuno
person.givenNamePaulo
person.givenNameZbynek
person.identifierR-000-10V
person.identifier.ciencia-id7818-2E25-9410
person.identifier.ciencia-id6219-8658-2307
person.identifier.ciencia-id0413-7328-BD68
person.identifier.orcid0000-0001-6929-8085
person.identifier.orcid0000-0002-4421-9958
person.identifier.orcid0000-0002-7318-6470
person.identifier.orcid0000-0002-6771-1304
person.identifier.orcid0000-0002-7813-1049
person.identifier.orcid0000-0001-5430-4403
person.identifier.orcid0000-0003-4185-7871
person.identifier.orcid0000-0002-3422-290X
person.identifier.orcid0000-0001-8256-6486
person.identifier.orcid0000-0002-3915-7270
person.identifier.ridE-5583-2016
person.identifier.ridA-5982-2015
person.identifier.ridG-6913-2018
person.identifier.ridD-1973-2013
person.identifier.scopus-author-id55681247100
person.identifier.scopus-author-id26029747600
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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