Breakthrough in Cancer Gene Therapy: Magnetic Hyperthermia Combines with Bioorthogonal Chemistry

Researchers from NOVA University Lisbon have discovered a promising new strategy in cancer gene therapy using magnetic hyperthermia combined with bioorthogonal chemistry to promote siRNA transfection against the IDO1 gene in dendritic cells. The study, published in Cancer Immunology, Immunotherapy, found that IDO1 silencing decreases around 70% in THP-1-derived dendritic cells and presents a silencing effect comparable to that attained with the gold standard Lipofectamine reagent, but with less cytotoxicity.

Key Takeaways:

• The study used magnetic nanoparticles functionalized with cyclooctyne moieties, which were attached to dendritic cell membranes engineered to express artificial azide receptors through strain-promoted azide-alkyne cycloaddition.
• Upon application of an alternating magnetic field, the nanoparticles generated heat and triggered thermal disruption of the cell membrane, promoting siRNA transfection against IDO1.
• IDO1 silencing promoted 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, creating a more immunogenic state.
• The study demonstrates the potential of magnetic hyperthermia-mediated transfection to enhance the intracellular delivery of silencing moieties in cells difficult to transfect, such as dendritic cells.

Statistics:

• IDO1 gene expression decreased by around 70% in THP-1-derived dendritic cells after magnetic hyperthermia-promoted transfection.
• The silencing effect of IDO1 gene expression was comparable to that attained with the gold standard Lipofectamine reagent, but with less cytotoxicity.
• The study was funded by the Fundação para a Ciência e a Tecnologia, European Commission, and Universidade Nova de Lisboa.

Sources:

• F. Ferreira et al. (2025). Heat up, silence on: IDO1 gene silencing in THP-1-derived dendritic cells triggered by magnetic hyperthermia. Cancer Immunology, Immunotherapy, 74(9):1-18. doi: 10.1007/s00262-025-04148-3
• NewsRx. Reports from NOVA University Lisbon Add New Data to Research in Cancer Gene Therapy (Heat up, silence on: IDO1 gene silencing in THP-1-derived dendritic cells triggered by magnetic hyperthermia). Cancer Weekly. September 9, 2025; p 57.