RT info:eu-repo/semantics/article
T1 Self-assembling ELR-based nanoparticles as smart drug-delivery systems modulating cellular growth via Akt
A1 González Valdivieso, Juan
A1 Girotti, Alessandra
A1 Muñoz Martínez, Raquel
A1 Rodríguez Cabello, José Carlos
A1 Arias Vallejo, Francisco Javier
K1 Elastin-like recombinamers
K1 Recombinantes tipo elastina
K1 Nanoparticles
K1 Nanopartículas
K1 Drug delivery
K1 Suministro de medicamentos
AB This work investigates the physicochemical properties and in vitro accuracy of a genetically engineered drug delivery system based on elastin-like block recombinamers. The DNA recombinant technics allowed us to create this smart complex polymer containing bioactive sequences for internalization, lysosome activation under acidic pH and blockage of cellular growth by a small peptide inhibitor. The recombinant polymer reversibly self-assembled, when temperature was increased above 15°C, into nanoparticles with a diameter of 72 nm and negative surface charge. Furthermore, smart nanoparticles were showed to enter in the cells via clathrin-dependent endocytosis, and properly blocked phosphorylation and consequent activation of Akt kinase. This system provoked apoptosis-mediated cell death in breast and colorectal cancer cells, which possess higher expression levels of Akt, whereas non-cancerous cells, such as endothelial cells, fibroblasts and mesenchymal stem cells, were not affected. Hence, we conclude that the conformational complexity of this smart elastin-like recombinamer leads to achieve successful drug delivery in targeted cells and could be a promising approach as nanocarriers with bioactive peptides in order to modulate multiple cellular processes involved in different diseases.
PB ACS Publications
SN 1526-4602
YR 2019
FD 2019
LK http://uvadoc.uva.es/handle/10324/36427
UL http://uvadoc.uva.es/handle/10324/36427
LA eng
NO Biomacromolecules, 2019, vol. 20, n. 5. p. 1996-2007
NO Producción Científica
DS UVaDOC
RD 23-nov-2024