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

View/ Open
Date
2021-08-04Author
da Silva, Emerson Rodrigo [UNIFESP]
Mello, Lucas Rodrigues de [UNIFESP]
Porosk, Ly
Lourenço, Thiago da Costa [UNIFESP]
Garcia, Bianca Bonetto Moreno [UNIFESP]
Costa, Carlos Alberto Rodrigues
Han, Sang Won [UNIFESP]
Souza, Juliana dos Santos de
Langel, Ülo
Type
ArtigoIs part of
ACS Applied Bio MaterialsDOI
https://doi.org/10.1021/acsabm.1c00601Metadata
Show full item recordAbstract
Cell-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.
Sponsorship
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Collections
- EPM - Artigos [17701]
Related items
Showing items related by title, author, creator and subject.
-
Encruzilhada. Artigos dos estudantes de arte contemporânea da Unifesp (2023)
Arantes, Pedro Fiori [UNIFESP]; Pires, Catarina Silva [UNIFESP]; Souza, Larissa Silva de [UNIFESP]; Miramontes, Luana [UNIFESP]; Jean, Marci [UNIFESP]; Alcarde, Yasmin Tainá Lana de [UNIFESP]; Lima, Ingrid Dos Santos [UNIFESP]; Costa, João Henrique Lopes da [UNIFESP]; Marques, Yago Maciel [UNIFESP]; Rocha, Romario Lopes [UNIFESP]; Gomes, Gustavo Bitencourt [UNIFESP]; Dias, Camila Oliveira [UNIFESP]; Santos, Thaynná Baltazar dos[UNIFESP]; Guedes, Beatriz [UNIFESP]; Melo, Gabriella [UNIFESP]; Francesquini, Maria Sueli de Camargo [UNIFESP]; Almeida, Raphael Gomes de [UNIFESP]; Morita, Yumi [UNIFESP]; Araújo, Isadora Trindade [UNIFESP]; Santo, Micaele Silva [UNIFESP]; Rocha, Karina Braga da [UNIFESP]; Campos, Maria Eduarda [UNIFESP]; Soares, Juliane Pereira [UNIFESP]; Silva, Gabrielly A. Santiago da [UNIFESP]; Lima, Gabrielle Pereira [UNIFESP]; Marzola, Ana Paula [UNIFESP]; Mões, Gustavo [UNIFESP]; Campos, Hellen [UNIFESP]; Baba, Luccas Ryoichi Kimura [UNIFESP]; Reis, Mariana [UNIFESP]; França, Milena [UNIFESP]; Yamaguchi, Ângela Harumi [UNIFESP]; Marassi, Beatriz [UNIFESP]; Porfirio, Beatriz [UNIFESP]; Mayumi, Cristiane [UNIFESP]; Agbanusi, Gladys Uju Balbino [UNIFESP]; Calixto, Fernanda [UNIFESP]; Capelli, Thalles [UNIFESP] (Universidade Federal de São Paulo, 2023)A arte contemporânea é, acima de tudo, multidisciplinar. A experimentação e a quebra de limites são primordiais para a existência desse campo tão vibrante e diversificado que permite que os artistas se expressem de forma ...
-
I Diretriz brasileira de cardio-oncologia pediátrica da Sociedade Brasileira de Cardiologia
Seber, Adriana [UNIFESP]; Miachon, Adriana Siviero [UNIFESP]; Tanaka, Ana Cristina Sayuri; Spinola-Castro, Angela Maria [UNIFESP]; Carvalho, Antonio Carlos [UNIFESP]; Petrilli, Antonio Sergio [UNIFESP]; Macedo, Carla Renata Pacheco Donato [UNIFESP]; Nars, Clarissa Carvalho Fongaro [UNIFESP]; Terzian, Claudia Naufel [UNIFESP]; Castro Junior, Claudio Galvão de; Santos, Cleusa Cavalcanti Lapa; Guerra, Cristina Chaves dos Santos; Silva, Dafne Cardoso Bourguignon da [UNIFESP]; Bassi, Débora Ugayama; Azeka, Estela; Feitosa, Fabiana Aragão; Hamamoto, Fernando [UNIFESP]; Szarf, Gilberto [UNIFESP]; Lederman, Henrique Manoel [UNIFESP]; Rigon Junior, Humberto João; Jatene, Ieda Biscegli; Mota, Isabele Coelho Fonseca da; Perrud, Jeferson Adriano [UNIFESP]; Soares Junior, José; Gutierrez, Julián Arango; Perin, Juliana Pepe Marinho [UNIFESP]; Soares, Juliana dos Santos [UNIFESP]; Catani, Liane Hulle; Tsai, Liliana Yu [UNIFESP]; Vianna, Livia Cristina [UNIFESP]; Paiva, Marcelo Goulart; Santos, Marcelo José; Ishigai, Marcia Marcelino de Souza [UNIFESP]; Diógenes, Maria Suely Bezerra [UNIFESP]; Alves, Maria Teresa de Seixas [UNIFESP]; Piedade, Maria Tereza Castro [UNIFESP]; Parreiras, Mariana; Cypriano, Mônica [UNIFESP]; Negrini, Nilce da Silva [UNIFESP]; Campos Filho, Orlando [UNIFESP]; Figueiredo, Paula Andrade [UNIFESP]; Novaes, Paulo Eduardo [UNIFESP]; Camargo, Paulo Roberto [UNIFESP]; Maia, Priscila dos Santos [UNIFESP]; Petrilli, Renata [UNIFESP]; Arduini, Rodrigo Genaro [UNIFESP]; Gouveia, Roseane Vasconcelos [UNIFESP]; Teruya, Suzana Barbosa Miranda [UNIFESP]; Moisés, Valdir Ambrósio [UNIFESP]; Morais, Vera Lúcia Lins de (Sociedade Brasileira de Cardiologia - SBC, 2013-05-01) -
Guerras culturais em verde e amarelo
Arantes, Pedro Fiori [UNIFESP]; Okuma, André [UNIFESP]; Nascimento, Giulia dos Santos [UNIFESP]; Melo, Keyla Vasconcelos de [UNIFESP]; Lorena, Diego [UNIFESP]; Alves, Amanda [UNIFESP]; Brait, Ana Laura [UNIFESP]; Alves, Gustavo Almeida [UNIFESP]; Fernandes, Cristina Naiara [UNIFESP]; Avelino, Larissa [UNIFESP]; Paloma, Oliveira [UNIFESP]; Bertellotti, André Zaparoli [UNIFESP]; Carreño, Rebeca Nieves Inostroza [UNIFESP]; Feo, Amanda [UNIFESP]; Andrade, Bruna [UNIFESP]; Garotti, Josiane [UNIFESP]; Flauto, Larissa [UNIFESP]; Tavares, Melissa [UNIFESP]; Barbosa, Ana Beatriz Tavares [UNIFESP]; Alejarra, Melissa Maria dos Santos [UNIFESP]; Santos, Nicole Pinheiro [UNIFESP]; Dourado, Kamilla [UNIFESP]; Silva, Pamela [UNIFESP]; Goyano, Lucius [UNIFESP]; Meneses, Maria Luiza [UNIFESP]; Ferreira, Gabriela [UNIFESP]; Monteiro, Paloma [UNIFESP]; Oliveira, Marcelo Lauton de [UNIFESP]; Paula, Patrícia Pinheiro Antunes de [UNIFESP]; Santos, Isabella Mendes dos [UNIFESP]; Borges, Júlia Rodrigues [UNIFESP] (Universidade Federal de São Paulo, 2022)Queridos/as leitores/as, bem-vindos/as ao nosso campo de batalha – e de estudos. Vocês estão prestes a ler um livro perigoso. Ele fala sobre muito do que estamos vivendo no Brasil dos últimos anos, olhando esse nosso ...