RT info:eu-repo/semantics/article
T1 CD44-targeted nanoparticles for co-delivery of docetaxel and an Akt inhibitor against colorectal cancer
A1 González Valdivieso, Juan
A1 Vallejo, Reinaldo
A1 Rodríguez Rojo, Soraya
A1 Santos García, María Mercedes
A1 Schneider Fontán, José
A1 Arias Vallejo, Francisco Javier
A1 Girotti, Alessandra
K1 Cáncer
K1 Nanomedicine
K1 Drug delivery
K1 Nanoparticles
K1 Biomaterials Elastin-like recombinamers (ELRs)
K1 Colorectal cancer (CRC)
K1 23 Química
K1 32 Ciencias Médicas
AB New strategies to develop drug-loaded nanocarriers with improved therapeutic efficacy are needed for cancer treatment. Herein we report a novel drug-delivery nanosystem comprising encapsulation of the chemotherapeutic drug docetaxel (DTX) and recombinant fusion of a small peptide inhibitor of Akt kinase within an elastinlike recombinamer (ELR) vehicle. This combined approach is also precisely targeted to colorectal cancer cells by means of a chemically conjugated DNA aptamer specific for the CD44 tumor marker. This 53 nm dual-approach nanosystem was found to selectively affect cell viability (2.5 % survival) and proliferation of colorectal cancer cells in vitro compared to endothelial cells (50 % survival), and to trigger both apoptosis- and necrosis-mediated cell death. Our findings also show that the nanohybrid particles remain stable under physiological conditions, trigger sustained drug release and possess an adequate pharmacokinetic profile after systemic intravenous administration. In vivo assays showed that these dual-approach nanohybrids significantly reduced the number of tumor polyps along the colorectal tract in a murine colorectal cancer model. Furthermore, systemic administration of advanced nanohybrids induced tissue recovery by improving the morphology of gastrointestinal crypts and the tissue architecture. Taken together, these findings indicate that our strategy of an advanced dualapproach nanosystem allows us to achieve successful controlled release of chemotherapeutics in cancer cells and may have a promising potential for colorectal cancer treatment.
PB Elservier
SN 2772-9508
YR 2024
FD 2024
LK https://uvadoc.uva.es/handle/10324/69269
UL https://uvadoc.uva.es/handle/10324/69269
LA eng
NO Biomaterials Advances, Noviembre, 2023, vol. 124
NO Producción Científica
DS UVaDOC
RD 22-dic-2024