PLGA-PEG-azide from PolySciTech used in development of nanoparticle-based diabetes treatment

 

In Type-1 diabetes an improper immune response attacks insulin-producing beta cells and destroys them leading to a dependence on external insulin. Generation of immune tolerance towards the B cells can prevent diabetes. Recently, researchers at University of North Carolina Chapel Hill and University of Texas Southwestern Medical Center used PLGA-PEG-Azide (Cat# AI091) from PolySciTech (www.polyscitech.com) to create a diabetes treatment which reduces immune attack against insulin-producing cells. This research holds promise to provide for a prophylactic against diabetes. Read more: Au, Kin Man, Roland Tisch, and Andrew Z. Wang. "In Vivo Bioengineering of Beta Cells with Immune Checkpoint Ligand as a Treatment for Early-Onset Type 1 Diabetes Mellitus." ACS nano (2021). https://pubs.acs.org/doi/abs/10.1021/acsnano.1c07538

“Abstract: Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by autoreactive T cells targeting the insulin-producing beta (β) cells. Despite advances in insulin therapy, T1DM still leads to high morbidity and mortality in patients. A key focus of T1DM research has been to identify strategies that re-establish self-tolerance and suppress ongoing autoimmunity. Here, we describe a strategy that utilizes pretargeting and glycochemistry to bioengineer β cells in situ to induce β-cell-specific tolerance. We hypothesized that β-cell-targeted Ac4ManNAz-encapsulated nanoparticles deliver and establish β cells with high levels of surface reactive azide groups. We further theorized that administration of a dibenzylcyclooctyne (DBCO)-functionalized programmed death-ligand 1 immunoglobulin fusion protein (PD-L1-Ig) can be readily conjugated to the surface of native β cells. Using nonobese diabetic (NOD) mice, we demonstrated that our strategy effectively and selectively conjugates PD-L1 onto β cells through bioorthogonal stain-promoted azide–alkyne cycloaddition. We also showed that the in vivo functionalized β cells simultaneously present islet-specific antigen and PD-L1 to the engaged T cells, reversing early onset T1DM by reducing IFN-gamma expressing cytotoxic toxic T cells and inducing antigen-specific tolerance. KEYWORDS: type 1 diabetes mellitus immune checkpoints pretargeting stain-promoted azide−alkyne cycloaddition immunotolerance”