Artículo del mes
marzo 2022

Smart ELR nanoparticles as advanced anti-Akt kinase delivery systems for pancreatic cancer therapy

Referencia artículo:
ACS Appl. Mater. Interfaces 2021, 13 (47): 55790–55805
En este trabajo se ha estudiado y demostrado por primera vez, el potencial antitumoral de nanopartículas poliméricas capaces de inhibir la kinasa Akt en modelos clínicamente relevantes derivados de pacientes con cáncer de páncreas. Las nanopartículas, de unos 70 nm de diámetro, liberan un péptido inhibidor de 15 aminoácidos que bloquea una ruta de señalización intracelular clave para la proliferación de las células pancreáticas tumorales, induciendo su entrada en apoptosis. Además, se estudió en ratones la farmacocinética, biodistribución y biocompatibilidad de las nanopartículas en órganos vitales.
Resumen
Pancreatic cancer is one of the deadliest cancers partly due to late diagnosis, poor drug delivery to the target site and acquired resistance to therapy. Therefore, more effective therapies are urgently needed to improve the outcome of patients. In this work, we have tested self-assembling genetically engineered polymeric nanoparticles formed by elastin-like recombinamers (ELRs), carrying a small peptide inhibitor of the protein kinase Akt, in both PANC-1 and patient-derived pancreatic cancer cells (PDX models). Nanoparticle cell uptake was measured by flow cytometry and subcellular localisation was determined by confocal microscopy, which showed a lysosomal localisation of these nanoparticles. Furthermore, metabolic activity and cell viability were significantly reduced after incubation with nanoparticles carrying the Akt inhibitor in a time- and dose-dependent fashion. Self-assembling 73 ± 3.2 nm size nanoparticles inhibited phosphorylation and consequent activation of Akt protein, blocked the NF-ĸB signalling pathway and triggered caspase 3-mediated apoptosis. Furthermore, in vivo assays showed that ELR-based nanoparticles were suitable devices for drug delivery purposes with long circulating time and minimum toxicity. Hence, the use of these smart nanoparticles could lead to the development of more effective treatment options for pancreatic cancer based on the inhibition of Akt.
Sobre el grupo investigador