[Theragnostic approaches using gold nanorods and near infrared light].

Gold nanoparticles have unique optical properties such as surface-plasmon and photothermal effects. Such properties have resulted in gold nanoparticles having several clinical applications. Gold nanorods (which are rod-shaped gold nanoparticles) show a surface plasmon band in the near-infrared region. They have therefore been proposed as contrast agents for bioimaging, or as heating devices for photothermal therapy. Polyethylene glycol-modified gold nanorods systemically administrated into mice can be detected with integrating sphere, and the stability of the gold nanorods in blood flow evaluated. After intravenous injection of gold nanorods followed by near-infrared laser irradiation, significant tumor damage triggered by the photothermal effect was observed. To deliver gold nanorods to the target tissue, thermosensitive polymer gel-coated gold nanorods were prepared. After intravenous injection of the gel-modified gold nanorods and irradiation of the tumor, a larger amount of gold was detected in the irradiated tumor than in the non-irradiated tumor. This effect is due to the hydrophobic interaction between the cellular membrane or the extracellular matrix and the gel surfaces induced by the photothermal effect. Furthermore, the photothermal effect enhanced the permeability of the stratum corneum of the skin. As a result of treatment of the skin with ovalbumin and gold nanorods followed by near-infrared light irradiation, a significant amount of protein was detected in the skin. The gold nanorods therefore showed several functions as a photothermal nanodevice for bioimaging, thermal therapy, and a drug delivery system.

Controlled release of PEG chain from gold nanorods: targeted delivery to tumor.

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.