title: Polyethylenimine-conjugated gold nanoparticles: Gene transfer potential and low toxicity in the cornea.
abstract: This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles (PEI2-GNPs) in the human cornea in vitro and rabbit cornea in vivo. PEI2-GNPs with nitrogen-to-phosphorus ratios of up to 180 exhibited significant transgene delivery in the human cornea without altering the viability or phenotype of these cells. Similarly, PEI2-GNPs applied to corneal tissues collected after 12 hours, 72 hours, or 7 days exhibited appreciable gold uptake throughout the rabbit stroma with gradual clearance of GNPs over time. Transmission electron microscopy detected GNPs in the keratocytes and the extracellular matrix of the rabbit corneas. Additionally, slit-lamp biomicroscopy in live animals even 7 days after topical PEI2-GNP application to the cornea detected no inflammation, redness, or edema in rabbit eyes in vivo, with only moderate cell death and immune reactions. These results suggest that PEI2-GNPs are safe for the cornea and can potentially be useful for corneal gene therapy in vivo.
  
  
  BACKGROUND
  This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles in the human cornea in vitro and rabbit cornea in vivo. The results suggest that PEI2-GNPs are safe for the cornea and can potentially be useful for corneal gene therapy in vivo.
authors.affiliation: Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Sharma
authors.forename: Ashish
authors.initials: A
authors.lastname: Tandon
authors.forename: Jonathan C K
authors.initials: JC
authors.lastname: Tovey
authors.forename: Rangan
authors.initials: R
authors.lastname: Gupta
authors.forename: J David
authors.initials: JD
authors.lastname: Robertson
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Fortune
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Klibanov
authors.forename: John W
authors.initials: JW
authors.lastname: Cowden
authors.forename: Frank G
authors.initials: FG
authors.lastname: Rieger
authors.forename: Rajiv R
authors.initials: RR
authors.lastname: Mohan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003315:Cornea / Q000166:cytology / Q000378:metabolism*; D060527:Corneal Keratocytes / Q000166:cytology / Q000187:drug effects; D005260:Female; D018014:Gene Transfer Techniques; D006046:Gold / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D053768:Metal Nanoparticles / Q000009:adverse effects* / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D011094:Polyethyleneimine / Q000737:chemistry*; D011817:Rabbits
chemical_list: D006046:Gold; D011094:Polyethyleneimine