ArticleMolecular therapy. Methods & clinical development2025
Anti-TNF-α antisense-oligonucleotide-conjugated PLG nanoparticles protect transplanted islets.
Article in Molecular therapy. Methods & clinical development, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
One of the many challenges for islet transplantation as a treatment for type 1 diabetes is inflammation that contributes to islet de-differentiation and death. Innate immune cells such as monocytes and macrophages secrete tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), inducible nitric oxide synthase (iNOS), and IL-6, which directly contribute to islet dysfunction. Attenuation of the early inflammatory response post-transplantation may protect cell survival and subsequent function. Herein, we investigate the development of anti-TNF-α antisense-oligonucleotide-conjugated polylactide-co-glycolide nanoparticles (PLG-aTNF-α NPs) as an anti-inflammatory therapy after stem-cell-derived islet transplantation. PLG-aTNF-α NPs are shelf stable and successfully reduce TNF-α secretion and expression in inflammatory macrophages. Synergy between the aTNF-α antisense oligonucleotide and the polylactide-co-glycolide NPs results in further knockdown of IL-1β, IL-6, iNOS, and IL-12
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