title: Controlled release of PEG chain from gold nanorods: targeted delivery to tumor.
abstract: Gold nanorods exhibit strong absorbance of light in the near infrared region, which penetrates deeply into tissues. Since the absorbed light energy is converted into heat, gold nanorods are expected to act as a contrast agent for in vivo bioimaging and as a thermal converter for photothermal therapy. To construct a gold nanorod targeted delivery system for tumor a peptide substrate for urokinase-type plasminogen activator (uPA), expressed specifically on malignant tumors, was inserted between the PEG chain and the surface of the gold nanorods. In other words, we constructed PEG-peptide-modified gold nanorods. After mixing the gold nanorods with uPA, the PEG chain was released from the surface of the gold and subsequently nanorod aggregation took place. The formation of the aggregation was monitored as a decrease in light absorption at 900 nm. Tumor homogenate induced a significant decrease in this absorption. Larger amount of the PEG-peptide-modified gold nanorods bound to cells expressing uPA in vitro compared with control gold nanorods, which had scrambled sequence of the peptide. The PEG-peptide-modified gold nanorods showed higher accumulation in tumor than the control after they were injected intravenously into tumor-bearing mice, however, the density of the peptide on the surface of the gold nanorods was a key factor of their biodistributions. This targeted delivery system, which responds to uPA activity, is expected to be a powerful tool for tumor bioimaging and photothermal tumor therapy.
authors.affiliation: Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan. niidome.takuro.655@m.kyushu-u.ac.jp
authors.forename: Takuro
authors.initials: T
authors.lastname: Niidome
authors.forename: Akira
authors.initials: A
authors.lastname: Ohga
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Kazuto
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yasuro
authors.initials: Y
authors.lastname: Niidome
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mori
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D000818:Animals; D004337:Drug Carriers; D006046:Gold / Q000737:chemistry*; D051379:Mice; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D010455:Peptides; D011092:Polyethylene Glycols; D006046:Gold; D014568:Urokinase-Type Plasminogen Activator