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A combination therapy consisting of two small interfering RNAs (siRNAs): one targeting **TGF-beta 1 (TGF-β1)** mRNA and the other targeting **COX-2 (Cyclooxygenase-2)** mRNA. The dual siRNA approach **simultaneously silences both genes**, leading to the downregulation of profibrotic and proinflammatory factors, induction of apoptosis in target cells (e.g., fibroblasts or tumor cells), reduced proliferation, migration, and invasion in preclinical models of hypertrophic scarring and cancer. This combination is often delivered using a nanoparticle carrier such as branched histidine-lysine polymers to enhance cellular uptake. In oncology, co-delivery can increase tumor T cell infiltration and augment the activity of immune checkpoint inhibitors, especially in hepatocellular carcinoma and other tumors characterized by TGF-β1/COX-2-mediated immune exclusion[1][2][3][4].
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