Modified gold nanoparticle vectors: A biocompatible intracellular delivery system for pancreatic islet cell transplantation

Abstract

Islet transplantation is an emerging therapy for type 1 diabetes mellitus with variable success. Molecular therapeutics is a promising approach to improve islet graft function and transplant outcomes. Traditional delivery vectors, however, have poor cell penetration and generally lead to compromised islet function. Modified gold nanoparticles represent a potential alternative in that they are taken up into cells efficiently and have unique binding properties. The objective of this study was to investigate whether gold nanoparticles can transfect islets uniformly without compromising cellular function. Cy5-oligonucleotide-conjugated gold nanoparticle islet transfection was evaluated using confocal microscopy and flow cytometry. Isolated mice and human islets were transfected and evaluated for mitochondrial potential changes, calcium influx, and insulin secretion in response to glucose challenge and in vivo graft function. Highly efficient gold nanoparticle uptake was observed. Transfected islets demonstrated normal mitochondrial function, calcium influx, and insulin release when stimulated by glucose. These islets produced a 100% diabetes cure rate after transplantation. Intraperitoneal glucose tolerance test demonstrated similar graft function as controls. We describe the development of a modified gold nanoparticle approach that allows for the efficient and nontoxic transfection of not only single cells but also more complex tissue architectures, such as pancreatic islets, both in vitro and in vivo.