Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles
In the present study, we designed a nanoscale platform for the sustained and controlled delivery of nutrients to pancreatic islets-upon transplantation.  Our platform consists of a mesoporous silica nanoparticle (MSNP), loaded with glutamine (G), an essential amino acid required for islet survival and function, and capped with polydopamine (PD). To control the release of glutamine, various concentrations (0.5 - 2 mg/mL) of PD and incubation times (0.5 – 2 h) with MSNPs were investigated in terms of pharmacological properties and biological functions. After extensive testing, PD-G-MSNPs made using PD coating of 0.5 mg/mL incubated for 0.5 h resulted in the optimal platform to maintain the islet viability and functionality in vitro. Following syngeneic renal sub-capsule islet transplantation in STZ-diabetic mice, PD-G-MSNPs improved the engraftment of pancreatic islets as well as their function, resulting in re-establishment of glycemic control. Collectively, our data shows that PD-G-MSNPs can support transplanted islets by providing them with a controlled and sustained supply of nutrients. Overall design: Aim of this study: investigate the protective effect of PD-G-MSNPs on mouse pancreatic islets following exposure to inflammatory cytokines. The work will include the relevant significant pathways (specifically, function and immune-realted pathways) up- and down-regulated in mouse pancreatic islets w/ and w/o PD-G-MSNPs following exposure to inflammatory cytokines (IL-1beta, TNF-alfa and IL6) for 48h. The experimental groups are three: healthy islets (control), islets inflammed, islets inflammed treated with PD-G-MSNPs. The experiment has been performed in triplicate.