Avaliação de novos ciclotideos com potencial anti câncer e nanoestruturações associadas

• Ano de defesa: 2015
• Autor(a) principal: Pinto, Michelle Flaviane Soares
• Orientador(a): Franco, Octávio Luiz
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Católica de Brasília
• Programa de Pós-Graduação: Programa Strictu Sensu em Ciências Genômicas e Biotecnologia
• Departamento: Escola de Saúde e Medicina
• País: Brasil
• Palavras-chave em Português: Ciclotídeos; Nanotecnologia; Biologia molecular; Câncer
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::GENETICA
• Link de acesso: https://bdtd.ucb.br:8443/jspui/handle/tede/2165

Cancer consists of a generic term applied to various diseases, presenting an uncontrolled growth of cells capable of invading tissues and organs and spread to other parts of the body. These cells tend to be very aggressive, uncontrolled, dividing rapidly and determining the tumors formation. Since cancer is one of the major causes of mortality and morbidity worldwide, it is necessary to discover new ways of treatment and new molecules that are less harmful than conventional therapies. Many alternatives aimed for screening anticancer peptides, seeking molecules in nature that can serve as new medicine. Among them are cyclotides, a multifunctional family of peptides characterized by C- to N-termini connection and for presenting a characteristic arrangement named cyclic cystein knot (CCK) stabilized by three bridges sulfide. In this work, we extracted and characterized the parigidinbr2 cyclotide, belonging to the family of the bracelets isolated from Palicourea rigida leaves, which unlike other cyclotides present its C- and N-termini free. The parigidin-br2 showed anticancer activity against both cell lines, MCF-7 (breast cancer) and CACO2 (colorectal adenocarcinoma) at concentrations of 10.5 μM and 5.25 μM, with no hemolytic activity at these concentrations. Additionally, the kalata B2 and parigidin-br1 cyclotides were nanostructured using polymers Eudragit® L 100-55 and RS 30 D (3: 1 w: w). Dynamic light scattering analysis show nanoparticles of 91 nm in diameter kalata B2 and 188 nm in diameter parigidin-br1. Furthermore, the encapsulation rate was 95% for both cyclotides. In vitro assays showed that the nanostructured cyclotides were capable of control the MCF-7 and CACO2 growth. Data here reported indicated that nanoformulated cyclotides showed anticancer activity, exhibiting sustained drug release, indicate that Eudragits® nanocapsules can be successfully utilized cyclotides delivery, generating delivery systems for cancer control.