title: Modified gold nanoparticle vectors: a biocompatible intracellular delivery system for pancreatic islet cell transplantation.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Divison of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Vega
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Tricia
authors.initials: T
authors.lastname: Harvat
authors.forename: Shusen
authors.initials: S
authors.lastname: Wang
authors.forename: Merigeng
authors.initials: M
authors.lastname: Qi
authors.forename: Adeola F
authors.initials: AF
authors.lastname: Adewola
authors.forename: Dongyoung
authors.initials: D
authors.lastname: Lee
authors.forename: Enrico
authors.initials: E
authors.lastname: Benedetti
authors.forename: Jose
authors.initials: J
authors.lastname: Oberholzer
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D006046:Gold; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D053758:Nanoparticles
chemical_list: D001672:Biocompatible Materials; D006046:Gold