Herein, we investigate the development of anti-TNFα antisense oligonucleotide conjugated PLG nanoparticles (PLG-aTNFα) as an anti-inflammatory therapy after stem cell derived islet transplantation. PLG-aTNFα NPs are shelf stable and successfully reduce TNFα secretion and expression in inflammatory macrophages. Synergy between the aTNFα ASO and the PLG NPs results in further knockdown of IL-1β, IL-6, iNOS, and IL-12 in vitro indicating PLG-aTNFα NPs may protect against the inflammatory cascade in vivo. In a diabetic mouse model, SC islets transplanted to the peritoneal fat were protected after treatment with PLG-aTNFα NPs compared PLG NPs alone. TNFα and IL-1β expression was reduced in mice treated with PLG-aTNFα NPs indicating inflammation was reduced after transplant. PLG-aTNFα NPs reduce TNFα and protect islets, supporting their potential use a therapeutic in islet transplantation.
