title: Biological evaluation of RGDfK-gold nanorod conjugates for prostate cancer treatment.
abstract: Selective delivery of gold nanorods (GNRs) to sites of prostate tumor angiogenesis is potentially advantageous for localized photothermal therapy. Here, we report the cellular uptake and biodistribution of GNRs surface functionalized with the cyclic RGDfK peptide. The GNRs were synthesized to have a surface plasmon resonance (SPR) peak at 800?nm and grafted with a thiolated poly(ethylene glycol) (PEG) corona with or without RGDfK. The binding and uptake of the targeted (RGDfK) and untargeted GNRs were evaluated in DU145 prostate cancer and human umbilical vein endothelial cells (HUVEC) by high-resolution dark field microscopy, inductively coupled plasma mass spectrometry (ICP-MS), and transmission electron microscopy (TEM). The biodistribution of both GNRs was then evaluated in prostate tumor bearing mice. Targeting of the RGDfK surface-modified GNRs was confirmed in vitro due to selective binding and uptake by endothelial cells. Tumor targeting was not observed in vivo, however, due to fast clearance of the RGDfK-GNRs from the blood. Further modifications of the nanoparticle?s surface properties are needed to enhance localization of the targetable system in sites of tumor angiogenesis.
authors.affiliation: Department of Bioengineering, Nano Institute of Utah, Salt Lake City, UT, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Gormley
authors.forename: Alexander
authors.initials: A
authors.lastname: Malugin
authors.forename: Abhijit
authors.initials: A
authors.lastname: Ray
authors.forename: Ryan
authors.initials: R
authors.lastname: Robinson
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006046:Gold / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D043942:Nanotubes; D009389:Neovascularization, Pathologic / Q000473:pathology; D010456:Peptides, Cyclic / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D013054:Spectrophotometry, Atomic; D013438:Sulfhydryl Compounds / Q000737:chemistry; D020349:Surface Plasmon Resonance; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D010456:Peptides, Cyclic; D013438:Sulfhydryl Compounds; C099250:cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl); D011092:Polyethylene Glycols; D006046:Gold
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