Diagnostic tool for Alzheimer’s disease based on a proprietary blood-brain barrier peptide shuttle-nanoparticle

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Publicações

Antimigratory and antiproliferative effects of the brain‐targeted peptide conjugate PepH3‐vCPP2319 on triple negative breast cancer cell cultures

Publication . Gonçalves, Catarina; Castanho, Miguel A. R. B.; Cavaco, Marco; Neves, Vera

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype affecting mostly younger women with a poor 5-year overall survival. It is characterized by a high metastization rate, particularly to the brain, where the blood-brain barrier (BBB) hinders the pharmaceuticals delivery. New anticancer drugs able to inhibit cell migration are required to effectively prevent the development of metastasis. PepH3-vCPP2319 (AGILKRW(Ahx)WRRRYRRWRRRRRQRRRPRR-amide), consisting of the conjugation of the BBB peptide shuttle (BBBpS) PepH3 (AGILKRW-amide) to the anticancer peptide (ACP) vCPP2319 (WRRRYRRWRRRRRQRRRPRR-amide), was reported to have high anticancer activity (IC50 = 5.0 μM) toward highly aggressive TNBC cells (MDA-MB-231) paired with 2-fold increased accumulation in the brain when compared to unconjugated vCPP2319. Herein, we demonstrate that PepH3-vCPP2319 inhibits cell migration and proliferation in wound healing assays, outperforming the gold standard small chemical inhibitor, iCRT-3. The concentration required to inhibit cell migration is 10-fold lower for PepH3-vCPP2319 (0.5 μM) when compared with iCRT-3 (50 μM). Likewise, PepH3-vCPP2319 at 2.5 μM was more efficient in preventing cell proliferation when compared with 50 μM iCRT-3, with 45% reduction in spheroid diameter. This study sheds light on the antimetastatic potential of PepH3-vCPP2319 through abrogation of cell migration to distant sites, including the brain.

2025Artigo científico

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The potential of peptide-based inhibitors in disrupting protein–protein interactions for targeted cancer therapy

Publication . Afonso, Alexandra L.; Cavaleiro, Catarina Tavares; Castanho, Miguel A. R. B.; Neves, Vera; Cavaco, Marco

Protein-protein interactions (PPIs) form an intricate cellular network known as the interactome, which is essential for various cellular processes, such as gene regulation, signal transduction, and metabolic pathways. The dysregulation of this network has been closely linked to various disease states. In cancer, these aberrant PPIs, termed oncogenic PPIs (OncoPPIs), are involved in tumour formation and proliferation. Therefore, the inhibition of OncoPPIs becomes a strategy for targeted cancer therapy. Small molecule inhibitors have been the dominant strategy for PPI inhibition owing to their small size and ability to cross cell membranes. However, peptide-based inhibitors have emerged as compelling alternatives, offering distinct advantages over small molecule inhibitors. Peptides, with their larger size and flexible backbones, can effectively engage with the broad interfaces of PPIs. Their high specificity, lower toxicity, and ease of modification make them promising candidates for targeted cancer therapy. Over the past decade, significant advancements have been made in developing peptide-based inhibitors. This review discusses the critical aspects of targeting PPIs, emphasizes the significance of OncoPPIs in cancer therapy, and explores the advantages of using peptide-based inhibitors as therapeutic agents. It also highlights recent progress in peptide design aimed at overcoming the limitations of peptide therapeutics, offering a comprehensive overview of the current landscape and potential of peptide-based inhibitors in cancer treatment.

2025Artigo científico

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Entidade financiadora

Fundação para a Ciência e a Tecnologia

Programa de financiamento

CEEC IND4ed

Número da atribuição

2021.00895.CEECIND/CP1673/CT0004