Amyloid-like self-assembly of a hydrophobic cell-penetrating peptide and its use as a carrier for nucleic acids

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dc.citation.issue8pt_BR
dc.citation.volume4pt_BR
dc.contributor.authorda Silva, Emerson Rodrigo [UNIFESP]
dc.contributor.authorMello, Lucas Rodrigues de [UNIFESP]
dc.contributor.authorPorosk, Ly
dc.contributor.authorLourenço, Thiago da Costa [UNIFESP]
dc.contributor.authorGarcia, Bianca Bonetto Moreno [UNIFESP]
dc.contributor.authorCosta, Carlos Alberto Rodrigues
dc.contributor.authorHan, Sang Won [UNIFESP]
dc.contributor.authorSouza, Juliana dos Santos de
dc.contributor.authorLangel, Ülo
dc.contributor.authorLatteshttp://lattes.cnpq.br/7800589206457326pt_BR
dc.contributor.authorLatteshttp://lattes.cnpq.br/4209242593570615
dc.contributor.authorLatteshttp://lattes.cnpq.br/4726216622634724
dc.contributor.authorLatteshttp://lattes.cnpq.br/7341563736516694
dc.contributor.authorLatteshttp://lattes.cnpq.br/2833950143696339
dc.contributor.authorLatteshttp://lattes.cnpq.br/0069955147703693
dc.contributor.authorLatteshttp://lattes.cnpq.br/7929949468269206
dc.date.accessioned2023-05-08T17:52:40Z
dc.date.available2023-05-08T17:52:40Z
dc.date.issued2021-08-04
dc.description.abstractCell-penetrating peptides (CPPs) are a topic subject potentially exploitable for creating new nanotherapeutics for the delivery of bioactive loads. These compounds are often classified into three major categories according to their physicochemical characteristics: cationic, amphiphilic, and hydrophobic. Among them, the group of hydrophobic CPPs has received increasing attention in recent years due to toxicity concerns posed by highly cationic CPPs. The hexapeptide PFVYLI (P: proline, F: phenylalanine, V: valine, Y: tyrosine, L: leucine and I: isoleucine), a fragment derived from the C-terminal portion of α1-antitrypsin, is a prototypal example of hydrophobic CPP. This sequence shows reduced cytotoxicity, capacity of nuclear localization, and its small size readily hints suitability as a building block to construct nanostructured materials. In this study, we examine the self-assembling properties of PFVYLI and investigate its ability to form non-covalent complexes with nucleic acids. By using a combination of biophysical tools including synchrotron small-angle X-ray scattering and atomic force microscopy-based infrared spectroscopy, we discovered that this CPP self-assembles into discrete nanofibrils with remarkable amyloidogenic features. Over the course of days, these fibrils coalesce into rod-like crystals that easily reach the micrometer range. Despite lacking cationic residues in the composition, PFVYLI forms non-covalent complexes with nucleic acids that retain -sheet pairing found in amyloid aggregates. In vitro vectorization experiments performed with double-stranded DNA fragments indicate that complexes promote the internalization of nucleic acids, revealing that tropism toward cell membranes is preserved upon complexation. On the other hand, transfection assays with splice-correction oligonucleotides (SCOs) for luciferase expression show limited bioactivity across a narrow concentration window, suggesting that propensity to form amyloidogenic aggregates may trigger endosomal entrapment. We anticipate that the findings presented here open perspectives for using this archetypical hydrophobic CPP in the fabrication of nanostructured scaffolds, which potentially integrate properties of amyloids and translocation capabilities of CPPs.en
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipID19/20907-7pt_BR
dc.format.extent6404–6416pt_BR
dc.identifierRua Três de Maiopt_BR
dc.identifier.doihttps://doi.org/10.1021/acsabm.1c00601
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/67462
dc.languageeng
dc.publisherAmerican Chemical Societyen
dc.relation.ispartofACS Applied Bio Materials
dc.rightsinfo:eu-repo/semantics/openAccesspt_BR
dc.subjectCell penetrating peptidept_BR
dc.subjectAmyloiden
dc.subjectAtomic force microscopyen
dc.subjectNanoparticleen
dc.titleAmyloid-like self-assembly of a hydrophobic cell-penetrating peptide and its use as a carrier for nucleic acidsen
dc.typeinfo:eu-repo/semantics/articlept_BR
unifesp.campusEscola Paulista de Medicina (EPM)pt_BR
unifesp.departamentoBiofísicapt_BR
unifesp.graduateProgramCiências Biológicas (Biologia Molecular)pt_BR
unifesp.knowledgeAreaBiofísicapt_BR
unifesp.researchAreaBiofísica molecularpt_BR
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