RT info:eu-repo/semantics/article
T1 Smart nanoparticles as advanced anti-Akt kinase delivery systems for pancreatic cancer therapy
A1 González Valdivieso, Juan
A1 García Sampedro, Andrés
A1 Hall, Andrew R.
A1 Girotti ., Alessandra
A1 Arias Vallejo, Francisco Javier
A1 Pereira, Stephen P.
A1 Acedo, Pilar
K1 nanoparticle
K1 drug delivery
K1 elastin-like recombinamer
K1 Akt
K1 pancreatic cancer
AB 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.
PB American Chemical Society
SN 1944-8244
YR 2021
FD 2021
LK https://uvadoc.uva.es/handle/10324/73865
UL https://uvadoc.uva.es/handle/10324/73865
LA eng
NO ACS Applied Materials & Interfaces, 2021, vol. 13, n. 47, p. 55790-55805
NO Producción Científica
DS UVaDOC
RD 22-ene-2025