Estevez, HectorGarcia-Calvo, EstefaniaÁlvarez-Fernández Garcia, RobertoSanchez-Diaz, RaquelLazcano, Juan JoséMartin, PilarLuque-Garcia, Jose L.2026-03-202026-03-202025-09J Drug Deliv Sci Technol. 2023.1773-2247https://hdl.handle.net/20.500.12105/27343Chitosan-stabilized selenium nanoparticles (Ch-SeNPs) are promising agents for cancer therapy due to their unique physicochemical properties, including spherical morphology and uniform size distribution. This study investigates the molecular mechanisms underlying their antitumoral effects, with a focus on the nuclear proteome. Quantitative proteomic analysis revealed 343 nuclear proteins, 47 of which showed significant changes following Ch-SeNPs treatment. Key regulators such as CDK1 and CDC5 were implicated in cell cycle arrest and tumor suppression pathways. Ch-SeNPs also affected processes including mRNA metabolism and cytoskeleton organization. In addition, Ch-SeNPs significantly inhibited tumor growth in a murine melanoma model, supporting their therapeutic potential.This work was supported by Ministerio de Ciencia, Innovacion y Universidades (MICIU) grants PID2020-114529RB-I00 and PID2023-150182OB-I00. PM is supported by grants from the Madrid Regional Government (S2022/BMD-7209-INTEGRAMUNE-CM) , MCIN-ISCIII-Fondo de Investigacion Sanitaria (PI22/01759) . Hector Estevez acknowledges Ministry of Science, Innovation and Universities from the Spanish Government for a pre-doctoral fellowship (PRE2018-084196) .engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/SILAC-based nuclear proteomics uncovers antitumor mechanisms of selenium nanoparticles with in vivo validation in a melanoma modelAttribution-NonCommercial-NoDerivatives 4.0 International10.1016/j.jddst.2025.107155Journal of Drug Delivery Science and Technologyopen access