Yukichi Horiguchi

Photothermal Reshaping of Gold Nanorods Depends on the Passivating Layers of the Nanorod Surfaces

Photothermal reshaping of gold nanorods was triggered by pulsed-laser irradiation. The efficiency of the reshaping was strongly dependent on the surface conditions of the gold nanorods. When the gold nanorods were dispersed in concentrated hexadecyltrimethylammonium bromide (CTAB), the gold nanorods were efficiently transformed into a phi-shape. By comparison when poly(styrene sulfonate), poly(vinylpyrrolidone), poly(ethylene glycol), or phosphatidylcholine layers were used, the CTAB layers were found to be a better thermal insulator that helped to enhance the photothermal reshaping of the gold nanorods.

Pharmacokinetics of core-polymerized, boron-conjugated micelles designed for boron neutron capture therapy for cancer

Core-polymerized and boron-conjugated micelles (PM micelles) were prepared by free radical copolymerization of a PEG-b-PLA block copolymer bearing an acetal group and a methacryloyl group (acetal-PEG-b-PLA-MA), with 1-(4-vinylbenzyl)-closo-carborane (VB-carborane), and the utility of these micelles as a tumor-targeted boron delivery system was investigated for boron neutron capture therapy (BNCT). Non-polymerized micelles (NPM micelles) that incorporated VB-carborane physically showed significant leakage of VB-carborane (ca. 50%) after 12 h incubation with 10% fetal bovine serum (FBS) at 37 °C. On the other hand, no leakage from the PM micelles was observed even after 48 h of incubation. To clarify the pharmacokinetics of the micelles, (125)I (radioisotope)-labeled PM and NPM micelles were administered to colon-26 tumor-bearing BALB/c mice. The (125)I-labeled PM micelles showed prolonged blood circulation (area under the concentration curve (AUC): 943.4) than the (125)I-labeled NPM micelles (AUC: 495.1), whereas tumor accumulation was similar for both types of micelles (AUC(PM micelle): 249.6, AUC(NPM micelle): 201.1). In contrast, the tumor accumulation of boron species in the PM micelles (AUC: 268.6) was 7-fold higher than the NPM micelles (AUC: 37.1), determined by ICP-AES. Thermal neutron irradiation yielded tumor growth suppression in the tumor-bearing mice treated with the PM micelles without reduction in body weight. On the basis of these data, the PM micelles represent a promising approach to the creation of boron carrier for BNCT.

Gd@C82 metallofullerenes for neutron capture therapy—fullerene solubilization by poly(ethylene glycol)-block-poly(2-(N, N-diethylamino)ethyl methacrylate) and resultant efficacy in vitro

Abstract Poly(ethylene glycol)-block-poly(2-(N,N-diethylamino)ethyl methacrylate) (PEG-b-PAMA) was found to solubilize fullerenes such as C60, and this technique was applied to metallofullerenes. Gd@C82 was easily dissolved in water in the presence of PEG-b-PAMA without any covalent derivatization, forming a transparent complex about 20–30 nm in diameter. Low cytotoxicity was confirmed in vitro. Neutron irradiation of cultured cells (colon-26 adenocarcinoma) with Gd@C82-PEG-b-PAMA-complexed nanoparticles showed effective cytotoxicity, indicating the effective emission of gamma rays and internal conversion electrons produced from the neutron capture reaction of Gd. This result suggests a potentially valuable approach to gadolinium-based neutron capture therapy.

Tumor growth suppression by gadolinium-neutron capture therapy using gadolinium-entrapped liposome as gadolinium delivery agent

Neutron capture therapy (NCT) is a promising non-invasive cancer therapy approach and some recent NCT research has focused on using compounds containing gadolinium as an alternative to currently used boron-10 considering several advantages that gadolinium offers compared to those of boron. In this study, we evaluated gadolinium-entrapped liposome compound as neutron capture therapy agent by in vivo experiment on colon-26 tumor-bearing mice. Gadolinium compound were injected intravenously via tail vein and allowed to accumulate into tumor site. Tumor samples were taken for quantitative analysis by ICP-MS at 2, 12, and 24 h after gadolinium compound injection. Highest gadolinium concentration was observed at about 2 h after gadolinium compound injection with an average of 40.3 μg/g of wet tumor tissue. We performed neutron irradiation at JRR-4 reactor facility of Japan Atomic Energy Research Institute in Tokaimura with average neutron fluence of 2×10¹² n/cm². The experimental results showed that the tumor growth suppression of gadolinium-injected irradiated group was revealed until about four times higher compared to the control group, and no significant weight loss were observed after treatment suggesting low systemic toxicity of this compound. The gadolinium-entrapped liposome will become one of the candidates for Gd delivery system on NCT.

Use of boron cluster-containing redox nanoparticles with ROS scavenging ability in boron neutron capture therapy to achieve high therapeutic efficiency and low adverse effects

A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance.

Pulsed-Laser Induced Fragmentation and Dissociation of DNA Immobilized on Gold Nanoparticles

ABSTRACT Plasmid DNA was immobilized on positively-charged gold nanoparticles (GNPs). Pulsed-laser irradiation induced fragmentation and dissociation of DNA from the GNP-DNA complexes. Dissociation of DNA without degradation was achieved when 80- mJ/pulse of laser light irradiated the GNP-DNA complexes.

High-performance surface acoustic wave immunosensing system on a PEG/aptamer hybridized surface.

Label-free immunoassay systems have the advantages of procedural simplicity and a low construction cost of surfaces for immunosensing. When label-free immunoassay systems are considered, the nonspecific adsorption of unwanted materials should be eliminated unless it aids in the detection of error. PEG is well-known as a blocking agent for the prevention of the adsorption of nonspecific binding materials when coimmobilized with ligands for targets such as antibodies and oligonucleotides. The construction strategy for PEG/ligand coimmobilized surfaces is an important point in the preparation of a high-performance assays because the physiological condition of the ligand depends strongly on its interaction with the PEG chain. In this report, we investigate the interaction between thrombin and a thrombin-binding aptamer (TBA) on a PEG/TBA coimmobilized surface by using a shear horizontal surface acoustic wave (SAW) sensor. The thrombin-TBA binding property shows remarkable differences with changes in the PEG density and the distance from the gold surface to the aptamer.

Intra-tumor distribution of metallofullerene using micro-particle induced X-ray emission (PIXE).

To clarify the intra tumor distribution of gadlinium containing fullerene (Gd@C82), micro particle induced X-ray emission (Micro-PIXE) analysis were performed. The tumor bearing BALB/c mice were injected Gd@C82 and subcutaneous tumors were taken from 48h after the intravenous injection. Using the Micro-PIXE method, we could visualize Gd intra tumor distribution. Therefore our results indicate the possibility that Micro-PIXE is useful technique for imaging the bioditribution of Gd, and Gd@C82 is potentially useful Gd carrier for NCT.

Sulfobetaine-terminated PEG improves the qualities of an immunosensing surface

Poly(ethylene glycol) (PEG) possessing a sulfobetaine (SB) moiety at one end and a pentaethylenehexamine (N6) at the other end (SB-PEG-N6) was newly synthesized as a blocking agent for immunosensing surfaces. The N6 moiety strongly coordinates on gold surfaces, facilitating the tethering of the PEG chain to the sensor chip surface, and leaves the SB moiety free. Non-specific adsorption of bovine serum albumin (BSA) was analyzed on the SB-PEG-N6 tethered surface and compared with the methoxy-PEG-N6 (M-PEG-N6) tethered surface using a surface plasmon resonance (SPR) sensor. Non-specific BSA adsorption decreased with decreasing PEG chain length on the SB-PEG tethered chain surface. Non-specific adsorption of BSA decreased as ionic strength increased on SB-PEG-N6 surfaces; this phenomenon was completely opposite to that observed with an M-PEG-N6 tethered chain surface. The results show that SB moieties located close to the gold surface perform well with regard to protein rejection. Actually, low-molecular weight alkane thiol SB (SB-SH) showed minimum BSA adsorption. To evaluate protein recognition efficacy on a PEGylated surface, an antibody (IgG) immobilized surface was then constructed on a gold sensor chip using SB-PEG-N6 as the blocking agent. The specific protein recognition efficacy of SB-PEG-N6/IgG co-immobilized surfaces was higher than that obtained using SB-SH/IgG co-immobilized surfaces. We conclude that SB-terminated PEG exhibits the optimal qualities of a blocking agent, as it possesses both high suppression efficacy of nonspecific protein adsorption and specific protein recognition ability.