Logo do repositório
 
Publicação

PepH3-modified nanocarriers for delivery of therapeutics across the blood-brain barrier

2025Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorSzecskó, Anikó
dc.contributor.authorMészáros, Mária
dc.contributor.authorSimões, Beatriz T.
dc.contributor.authorCavaco, Marco
dc.contributor.authorChaparro, Catarina
dc.contributor.authorPorkoláb, Gergő
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorDeli, Mária A.
dc.contributor.authorNeves, Vera
dc.contributor.authorVeszelka, Szilvia
dc.date.accessioned2025-06-11T13:45:54Z
dc.date.available2025-06-11T13:45:54Z
dc.date.issued2025
dc.description© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.pt_PT
dc.description.abstractBackground: Nanocarriers targeting the blood-brain barrier (BBB) are promising drug delivery systems to enhance the penetration of therapeutic molecules into the brain. Immunotherapy, particularly monoclonal antibodies designed to bind amyloid-beta peptides have become a promising strategy for Alzheimer's disease, but ensuring efficacy and safety is challenging and crucial for these therapies. Our aim was to develop an innovative nanocarriers conjugated with PepH3, a cationic peptide derived from Dengue virus type-2 capsid protein that crosses the BBB and acts as a shuttle peptide for the encapsulated single domain antibody (sdAb) recognizing Aβ oligomers. Results: PepH3 peptide enhanced the uptake of the nanoparticles (NPs) into brain endothelial cells, and transcytosis of sdAb, as a potential therapeutic molecule, across both rat and human BBB culture models. The cargo uptake was a temperature dependent active process that was reduced by metabolic and endocytosis inhibitors. The cellular uptake of the cationic PepH3-tagged NPs decreased when the negative surface charge of brain endothelial cells became more positive after treatments with a cationic lipid or with neuraminidase by digesting the glycocalyx. The NPs colocalized mostly with endoplasmic reticulum and Golgi apparatus and not with lysosomes, indicating the cargo may avoid cellular degradation. Conclusions: Our results support that combination of NPs with a potential brain shuttle peptide such as PepH3 peptide can improve the delivery of antibody fragments across the BBB.pt_PT
dc.description.sponsorshipOpen access funding provided by HUN-REN Biological Research Centre, Szeged. This work was funded by grant from the National Research, Development and Innovation Office of Hungary (2018 − 2.1.15-TÉT-PT-2018-00013). S.V. was supported by the project no.143233, which has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the FK_22 funding scheme. M.M. was supported by the research grant (PD 138930) of the National Research, Development and Innovation Office, A.S. was supported by ÚNKP-23-3-SZTE-517 and Gedeon Richter Talentum Foundation. The authors VN, MARBC, MC, BS, thank the Portuguese Funding Agency, Fundação para a Ciência e a Tecnologia, FCT IP, for financial support (FCT/NKFIH, 2019/2020; PTDC/BTM-MAT/2472/2021).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFluids Barriers CNS . 2025 Apr 1;22(1):31pt_PT
dc.identifier.doi10.1186/s12987-025-00641-0pt_PT
dc.identifier.eissn2045-8118
dc.identifier.urihttp://hdl.handle.net/10400.5/101492
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationFCT/NKFIH, 2019/2020pt_PT
dc.relation.publisherversionhttps://fluidsbarrierscns.biomedcentral.com/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectBlood-brain barrierpt_PT
dc.subjectBrain deliverypt_PT
dc.subjectNanoparticlept_PT
dc.subjectPepH3pt_PT
dc.subjectSingle domain antibodypt_PT
dc.titlePepH3-modified nanocarriers for delivery of therapeutics across the blood-brain barrierpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBTM-MAT%2F2472%2F2021/PT
oaire.citation.issue1pt_PT
oaire.citation.titleFluids and Barriers of the CNSpt_PT
oaire.citation.volume22pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameTraguedo Simões
person.familyNameCavaco
person.familyNameChaparro
person.familyNameCastanho
person.familyNameNeves
person.givenNameBeatriz
person.givenNameMarco
person.givenNameCatarina
person.givenNameMiguel
person.givenNameVera
person.identifier1069324
person.identifier953259
person.identifier.ciencia-id3216-5E8A-7C4F
person.identifier.ciencia-id1412-63B8-7494
person.identifier.ciencia-id941B-C02A-C629
person.identifier.ciencia-id671C-1860-A160
person.identifier.orcid0000-0001-7880-7718
person.identifier.orcid0000-0002-0938-9038
person.identifier.orcid0000-0002-4030-2519
person.identifier.orcid0000-0001-7891-7562
person.identifier.orcid0000-0002-2989-7208
person.identifier.ridO-2176-2018
person.identifier.scopus-author-id56605575600
person.identifier.scopus-author-id26537945300
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationc02ad128-9387-43ac-a942-0f9fd28f6401
relation.isAuthorOfPublicationce7bbed1-4210-464f-93ac-f270ca7d2140
relation.isAuthorOfPublication391cbd1a-5c37-4c95-8b6d-1a494dc85019
relation.isAuthorOfPublicationf5e46f85-fabf-450a-9ee2-1c7b59410892
relation.isAuthorOfPublicationf62bb731-3f4d-4eaf-bc6b-dd379f6c2327
relation.isAuthorOfPublication.latestForDiscoveryf62bb731-3f4d-4eaf-bc6b-dd379f6c2327
relation.isProjectOfPublication53a00574-2785-453c-bd31-f54e9661b033
relation.isProjectOfPublication.latestForDiscovery53a00574-2785-453c-bd31-f54e9661b033

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
PepH3.pdf
Tamanho:
5.71 MB
Formato:
Adobe Portable Document Format
Ver/Abrir
Licença
A mostrar 1 - 1 de 1
Miniatura indisponível
Nome:
license.txt
Tamanho:
1.2 KB
Formato:
Item-specific license agreed upon to submission
Descrição:
Ver/Abrir

Coleções

FM - Artigos em Revistas Internacionais
IMM - Artigos em Revistas Internacionais