2026-05-05T10:16:29Zhttps://uvadoc.uva.es/oai/request
oai:uvadoc.uva.es:10324/738652025-01-17T07:12:10Zcom_10324_1134com_10324_931com_10324_894col_10324_1213
UVaDOC author González Valdivieso, Juan author García Sampedro, Andrés author Hall, Andrew R. author Girotti ., Alessandra author Arias Vallejo, Francisco Javier author Pereira, Stephen P. author Acedo, Pilar 2025-01-15T10:55:12Z 2025-01-15T10:55:12Z 2021 ACS Applied Materials & Interfaces, 2021, vol. 13, n. 47, p. 55790-55805 1944-8244 https://uvadoc.uva.es/handle/10324/73865 10.1021/acsami.1c14592 55790 47 55805 ACS Applied Materials & Interfaces 13 1944-8252 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 localization was determined by confocal microscopy, which showed a lysosomal localization 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-κB signaling 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. eng Attribution-NonCommercial-NoDerivatives 4.0 Internacional Smart nanoparticles as advanced anti-Akt kinase delivery systems for pancreatic cancer therapy info:eu-repo/semantics/article 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URL https://uvadoc.uva.es/bitstream/10324/73865/1/smart-nanoparticles-advanced-anti-akt-kinase-delivery-systems_preprint.pdf File MD5 daaeebe2804d820a71d33a6ce26cfcb3 2526902 application/pdf smart-nanoparticles-advanced-anti-akt-kinase-delivery-systems_preprint.pdf