No abstract

Controlled-release systems that respond to external stimuli have received great interest for use in medical treatments such as for drug delivery to specific sites. Gold nanorods have an absorption band at the near-infrared region and convert the absorbed light energy into heat, which is known as a "photothermal effect". Therefore, gold nanorods are expected to act not only as an on-demand thermal converter for photothermal therapy but also as a controller of a drug-release system capable of responding to the near-infrared light irradiation. In this study, to construct a controlled-release system that responds to near-infrared light irradiation, we modified gold nanorods with polyethylene glycol (PEG) through Diels-Alder cycloadducts. When the modified gold nanorods were irradiated by near-infrared light, the PEG chains were released from the gold nanorods because of the retro Diels-Alder reaction induced by the photothermal effect. As a result of the PEG release, the gold nanorods formed aggregates. This type of controlled-release system coupled with the aggregate formation of the gold nanorods triggered by near-infrared light could be expanded to applications of gold nanorods in medical fields such as drug and photothermal therapy.

Gold nanorods were modified with two types of doublestranded DNAs (dsDNA) with different melting temperatures. Irradiated by near-infrared laser light, the modified gold nanorods were heated, and single-stranded DNAs were released faster from the dsDNA with the lower melting temperature. Such combinations of different kinds of dsDNA allow us to construct a two-step release system of different types of oligonucleotides.Functional oligonucleotides, e.g., small interfering RNA (siRNA) and antisense and decoy oligonucleotides are expected as drugs that control gene expression and protein function. Controlled release systems for such oligonucleotides are essential for therapeutic application. External stimuli and the microenvironment of the affected part can be used as triggers for the controlled release system. Ultrasound, radio waves, and light have been used as external stimuli. 15 The acidic environments in tumor tissue and inside of endocytotic vesicles in cells have attracted attention as triggers of controlled release. 6 Proteases, such as matrix metalloproteinases that are overexpressed in tumor tissue, can also act as a trigger. 7 Gold nanorods are rod-shaped gold nanoparticles and have an absorption band in the near-infrared region 8 attributed to longitudinal surface plasmon resonance. Near-infrared light can deeply penetrate the human body because the near-infrared light region is located between strong absorption bands of water and hemoproteins. Gold nanorods can convert absorbed light energy to heat energy by the photothermal effect. Because of these unique properties, gold nanorods are expected to be developed as thermal converters for photothermal therapy. 9,10 Previously, we constructed a controlled release system of oligonucleotide from gold nanorods that responded to near-infrared laser irradiation. 11 In this system, we used double-stranded DNA (dsDNA)-modified gold nanorods. When the modified nanorods were illuminated with near-infrared laser light, they were heated, and single-stranded DNA (ssDNA) was released. In this study, to elucidate how the melting temperature of dsDNA affects the release efficiency of ssDNA, gold nanorods were modified with two kinds of dsDNAs with different melting temperatures. The release efficiencies of the ssDNAs from the gold surface were evaluated.dsDNA-modified gold nanorods were prepared as described in our previous report. 11 Briefly, thiol-terminated poly(ethylene glycol) (m-PEG 20000 -SH) was modified on the surface of gold nanorods via AuS bonds. The PEG-modified gold nanorods were coated with a silica layer using the Stöber method 12,13 (silica-coated gold nanorods). To introduce primary and secondary amino groups to the surface, branched-poly(ethyleneimine) (PEI) was coated on the surface of the silica-coated gold nanorods (PEI-coated gold nanorods) via electrostatic interaction between the negative charge of the silica layer and the positive charge of PEI. Finally, two types of dsDNAs with different melting temperatures (dsDNA Tm61 and dsDNA Tm80 , see Supp...

Gold nanorods, rod-shaped gold nanoparticles, have transverse and longitudinal surface plasmon (SP) bands at visible and near-infrared (IR) regions, respectively. Since the absorbed light energy is converted into heat, photothermal effect of gold nanorods can be triggered without damaging the tissues in the path of near-IR laser light. In this study, we tried to construct controlled release system of functional molecules from surface of gold nanorods mediated by the photothermal effect. First, we evaluated controlled release of poly(ethyleneglycol) (PEG) chains from PEG-modified gold nanorods (PEG-NR). Next, we employed double stranded oligonucleotide as a thermo-responsive dissociating group (DNA-NR). Finally, we evaluated photothermal release of PEG chains mediated retro-Diels-Alder reaction (PEG-DA-NR). For construction of controlled release system of functional molecules, these studies will provide important information about the photothermal reactions of surface molecules on the gold nanorods triggered by near-IR light irradiation.