RT Journal Article
T1 Mechanistic insights into the antitumoral potential and in vivo antiproliferative efficacy of a silver-based core@shell nanosystem
A1 Aragoneses Cazorla, Guillermo
A1 Álvarez-Fernández García, Roberto
A1 Martínez López, Angelica
A1 Gómez Gómez, María Milagros
A1 Vallet Regí, María Dulce Nombre
A1 Castillo Lluva, Sonia
A1 González Ortiz, Blanca
A1 Luque García, José Luis
AB This study delves into the biomolecular mechanisms underlying the antitumoral efficacy of a hybrid nanosystem, comprised of a silver core@shell (Ag@MSNs) functionalized with transferrin (Tf). Employing a SILAC proteomics strategy, we identified over 150 de-regulated proteins following exposure to the nanosystem. These proteins play pivotal roles in diverse cellular processes, including mitochondrial fission, calcium homeostasis, endoplasmic reticulum (ER) stress, oxidative stress response, migration, invasion, protein synthesis, RNA maturation, chemoresistance, and cellular proliferation. Rigorous validation of key findings substantiates that the nanosystem elicits its antitumoral effects by activating mitochondrial fission, leading to disruptions in calcium homeostasis, as corroborated by RT-qPCR and flow cytometry analyses. Additionally, induction of ER stress was validated through western blotting of ER stress markers. The cytotoxic action of the nanosystem was further affirmed through the generation of cytosolic and mitochondrial reactive oxygen species (ROS). Finally, in vivo experiments using a chicken embryo model not only confirmed the antitumoral capacity of the nanosystem, but also demonstrated its efficacy in reducing cellular proliferation. These comprehensive findings endorse the potential of the designed Ag@MSNs-Tf nanosystem as a  roundbreaking chemotherapeutic agent, shedding light on its multifaceted mechanisms and in vivo applicability.
SN 0378-5173
YR 2024
FD 2024-03-12
LK https://hdl.handle.net/20.500.14352/102711
UL https://hdl.handle.net/20.500.14352/102711
LA eng
NO Ministerio de Ciencia e Innovación
NO European Uniońs through ERC2015-AdG (VERDI) Proposal No. 694160
DS Docta Complutense
RD 18 abr 2025