000162555 001__ 162555
000162555 005__ 20260112133141.0
000162555 0247_ $$2doi$$a10.1007/s00262-025-04148-3
000162555 0248_ $$2sideral$$a145116
000162555 037__ $$aART-2025-145116
000162555 041__ $$aeng
000162555 100__ $$aFerreira, Daniela
000162555 245__ $$aHeat up, silence on: IDO1 gene silencing in THP‑1‑derived dendritic cells triggered by magnetic hyperthermia
000162555 260__ $$c2025
000162555 5060_ $$aAccess copy available to the general public$$fUnrestricted
000162555 5203_ $$aDendritic cells (DCs) are well-known antigen-presenting cells which have an important role in cancer immunomodulation due to the effective regulation of immune responses in the tumor microenvironment (TME). Indoleamine 2,3-dioxygenase 1 gene (IDO1) is upregulated in many types of cancers and associated with a poor prognosis, contributing to an immunosuppressive TME. IDO1 silencing in DCs is considered a promising new strategy in gene therapy owing to their capability to regulate T cells function and activation. This study focuses on the use of magnetic hyperthermia (MH) combined with bioorthogonal chemistry to promote siRNA transfection against IDO1 in THP-1-derived DCs. Magnetic nanoparticles (MNPs) functionalized with cyclooctyne moieties were attached by strain-promoted azide-alkyne cycloaddition to DCs membranes engineered to express artificial azide receptors. Upon the application of an alternating magnetic field, the MNPs generate heat and trigger the thermal disruption of the cell membrane. Results show that IDO1 gene expression decreases around 70% in THP-1-derived DCs, and that the MH-promoted transfection presents a silencing effect comparable to that attained with a gold standard Lipofectamine reagent, but with less cytotoxicity. Additionally, IDO1 silencing promotes the upregulation of mRNA levels of pro-inflammatory cytokines IL-6, TNF-α and IL-12A, and the downregulation of anti-inflammatory cytokine IL-10, providing a more immunogenic state which may lead to THP-1-derived DCs activation for future T cells antitumor response. Our findings reveal the potential of MH-mediated transfection to enhance the intracellular delivery of silencing moieties in cells difficult to transfect, such as DCs, as well as demonstrate the possibility of silencing IDO1 gene to overcome the immunosuppressive barrier imposed by the TME for cancer therapy.
000162555 536__ $$9info:eu-repo/grantAgreement/ES/MICIU/CNS2023-144436$$9info:eu-repo/grantAgreement/ES/MCIU/RYC2015-17640$$9info:eu-repo/grantAgreement/ES/MCIU/PCIN-2017-060$$9info:eu-repo/grantAgreement/EUR/ERA-NET-COFUND/MagicCellGene Project 2016$$9info:eu-repo/grantAgreement/ES/DGA/E15-23R
000162555 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000162555 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000162555 700__ $$0(orcid)0000-0003-0641-3407$$aAsín, Laura$$uUniversidad de Zaragoza
000162555 700__ $$0(orcid)0000-0002-3373-9341$$aIdiago-López, Javier
000162555 700__ $$0(orcid)0000-0001-6170-4237$$aGrazú, Valeria
000162555 700__ $$0(orcid)0000-0003-1081-8482$$aMartínez de la Fuente, Jesús
000162555 700__ $$0(orcid)0000-0001-5559-8757$$aFratila, Raluca M.
000162555 700__ $$aBaptista, Pedro V.
000162555 700__ $$aFernandes, Alexandra R.
000162555 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000162555 773__ $$g74 (2025), 292 [18 pp.]$$pCancer immunol. immunother.$$tCANCER IMMUNOLOGY IMMUNOTHERAPY$$x0340-7004
000162555 8564_ $$s1779235$$uhttps://zaguan.unizar.es/record/162555/files/texto_completo.pdf$$yVersión publicada
000162555 8564_ $$s2142047$$uhttps://zaguan.unizar.es/record/162555/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000162555 909CO $$ooai:zaguan.unizar.es:162555$$particulos$$pdriver
000162555 951__ $$a2026-01-12-12:35:46
000162555 980__ $$aARTICLE