title: Targeting B16 tumors in vivo with peptide-conjugated gold nanoparticles.
abstract: This study examines the effects of polyethylene glycol (PEG) and peptide conjugation on the biodistribution of ultrasmall (2.7 nm) gold nanoparticles in mice bearing B16 melanoma allografts. Nanoparticles were delivered intravenously, and biodistribution was measured at specific timepoints by organ digestion and inductively coupled plasma mass spectrometry. All major organs were examined. Two peptides were tested: the cyclic RGD peptide (cRGD, which targets integrins); and a recently described peptide derived from the myxoma virus. We found the greatest specific tumor delivery using the myxoma peptide, with or without PEGylation. Un-PEGylated cRGD performed poorly, but PEGylated RGD showed a significant transient collection in the tumor. Liver and kidney were the primary targets of all constructs. None of the particles were able to cross the blood-brain barrier. Although it was able to deliver Au to B16 cells, the myxoma peptide did not show any cytotoxic activity against these cells, in contrast to previous reports. These results indicate that the effect of passive targeting by PEGylation and active targeting by peptides can be independent or combined, and that they should be evaluated on a case-by-case basis when designing new nanosystems for targeted therapies. Both myxoma peptide and cRGD should be considered for specific targeting to melanoma, but a thorough investigation of the cytotoxicity of the myxoma peptide to different cell lines remains to be performed.
authors.affiliation: Department of Biomedical Engineering, McGill University, 3775 University St., Montreal QC H3A 2B4, Canada.
authors.forename: Wilson
authors.initials: W
authors.lastname: Poon
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Devesh
authors.initials: D
authors.lastname: Bekah
authors.forename: Jose G
authors.initials: JG
authors.lastname: Teodoro
authors.forename: Jay L
authors.initials: JL
authors.lastname: Nadeau
mesh_terms: D064591:Allografts; D000818:Animals; D001826:Body Fluids / Q000737:chemistry; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006046:Gold / Q000737:chemistry* / Q000493:pharmacokinetics; D008546:Melanoma, Experimental / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D009233:Myxoma virus / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics*; D010456:Peptides, Cyclic / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D010455:Peptides; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; D011092:Polyethylene Glycols; D006046:Gold