cAmbly: A non-toxic cell-penetrating peptide derived from Amblyomin-X with targeted delivery to mitochondrial and cytoplasmic proteins

Autor(es)

Buri, Marcus Vinicius ; Garavelli, Graciana Yokota ; Vigerelli, Hugo ; de Souza, Marcelo Medina ; Maia Lobba, Aline Ramos ; Ghidelli-Disse, Sonja ; Chudzinski-Tavassi, Ana Marisa

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 20, n. 3, p. 14-pg., 2025-03-12.

Resumo

The effective delivery of drugs remains a major challenge in the development of new therapeutic molecules. Several strategies have been employed to address this issue, with cell-penetrating peptides (CPPs) standing out due to their ability to traverse cell membranes with minimal cytotoxicity and their relatively straightforward synthesis when conjugated with other molecules. However, while CPPs can successfully enter the cytoplasm, they often lack specificity for particular organelles, leaving target engagement to the drug itself. In this study, we present cAmbly, a novel CPP derived from the antitumoral protein Amblyomin-X. Our findings demonstrate that cAmbly efficiently internalizes into T98G cells within 30 min of incubation and preferentially colocalizes with mitochondria, exhibiting a clear affinity for mitochondrial proteins. These results suggest that cAmbly could serve as a promising delivery vehicle for mitochondria-targeted drugs, such as BCL-2 or OXPHOS modulators, which are commonly employed in cancer treatment. Furthermore, we identified the C-terminal of cAmbly as the optimal site for conjugating molecules intended for intracellular delivery. (AU)

• Processo FAPESP: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
• Beneficiário: Ana Marisa Chudzinski-Tavassi
• Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia
• Processo FAPESP: 20/13139-0 - Centro de Excelência na Descoberta de Novos Alvos
• Beneficiário: Ana Marisa Chudzinski-Tavassi
• Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia
• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs