Hiroaki Akasaka

Bio: Hiroaki Akasaka is an academic researcher from Kobe University. The author has contributed to research in topics: In vivo & Dosimeter. The author has an hindex of 9, co-authored 34 publications receiving 233 citations.

Titanium peroxide nanoparticles enhanced cytotoxic effects of X-ray irradiation against pancreatic cancer model through reactive oxygen species generation in vitro and in vivo

Abstract: Biological applications of nanoparticles are rapidly increasing, which introduces new possibilities to improve the efficacy of radiotherapy. Here, we synthesized titanium peroxide nanoparticles (TiOxNPs) and investigated their efficacy as novel agents that can potently enhance the effects of radiation in the treatment of pancreatic cancer. TiOxNPs and polyacrylic acid-modified TiOxNPs (PAA-TiOxNPs) were synthesized from anatase-type titanium dioxide nanoparticles (TiO2NPs). The size and morphology of the PAA-TiOxNPs was evaluated using transmission electron microscopy and dynamic light scattering. The crystalline structures of the TiO2NPs and PAA-TiOxNPs with and without X-ray irradiation were analyzed using X-ray absorption. The ability of TiOxNPs and PAA-TiOxNPs to produce reactive oxygen species in response to X-ray irradiation was evaluated in a cell-free system and confirmed by flow cytometric analysis in vitro. DNA damage after X-ray exposure with or without PAA-TiOxNPs was assessed by immunohistochemical analysis of γ-H2AX foci formation in vitro and in vivo. Cytotoxicity was evaluated by a colony forming assay in vitro. Xenografts were prepared using human pancreatic cancer MIAPaCa-2 cells and used to evaluate the inhibition of tumor growth caused by X-ray exposure, PAA-TiOxNPs, and the combination of the two. The core structures of the PAA-TiOxNPs were found to be of the anatase type. The TiOxNPs and PAA-TiOxNPs showed a distinct ability to produce hydroxyl radicals in response to X-ray irradiation in a dose- and concentration-dependent manner, whereas the TiO2NPs did not. At the highest concentration of TiOxNPs, the amount of hydroxyl radicals increased by >8.5-fold following treatment with 30 Gy of radiation. The absorption of PAA-TiOxNPs enhanced DNA damage and resulted in higher cytotoxicity in response to X-ray irradiation in vitro. The combination of the PAA-TiOxNPs and X-ray irradiation induced significantly stronger tumor growth inhibition compared to treatment with either PAA-TiOxNPs or X-ray alone (p < 0.05). No apparent toxicity or weight loss was observed for 43 days after irradiation. TiOxNPs are potential agents for enhancing the effects of radiation on pancreatic cancer and act via hydroxyl radical production; owing to this ability, they can be used for pancreatic cancer therapy in the future.

MGDG extracted from spinach enhances the cytotoxicity of radiation in pancreatic cancer cells.

Abstract: In our previous study, monogalactosyl diacylglycerol (MGDG) purified from spinach was found to have cytotoxic effects in human cancer cell lines. This study further assessed whether MGDG can enhance the cytotoxic effects of radiation in human pancreatic cancer cells in vitro and in vivo. Glycoglycerolipids from spinach including MGDG were extracted from dried spinach. The cytotoxicity of MGDG were evaluated by the MTT assay using four human pancreatic cancer cell lines (MIAPaCa-2, AsPC-1, BxPC-3 and PANC-1) and normal human dermal fibroblasts (NHDFs). The effects of radiation and MGDG alone or in combination in MIAPaCa-2 cells was analyzed with the colony forming and apoptosis assays, western blotting and cell cycle and DNA damage analyses (γ-H2AX foci staining and comet assay). The inhibitory effects on tumor growth were assessed in a mouse xenograft tumor model. MGDG showed dose- and time-dependent cytotoxicity, with half-maximal inhibitory concentrations (IC50) in PANC-1, BxPC-3, MIAPaCa-2 and AsPC-1 cells at 72 h of 25.6 ± 2.5, 26.9 ± 1.3, 18.5 ± 1.7, and 22.7 ± 1.9 μM, respectively. The colony forming assay revealed fewer MIAPaCa-2, BxPC-3 and AsPC-1 cell colonies upon treatment with both MGDG and radiation as compared to irradiation alone (P < 0.05). The combination of MGDG and radiation induced a higher proportion of apoptosis in MIAPaCa-2 cells; this effect was associated with increased mitochondrial release of cytochrome c and activation of cleaved poly (ADP-ribose) polymerase and caspase-3. DNA damage was detected and DNA repair mechanisms were more frequently impaired in cells receiving the combination treatment as compared to either one alone. Tumor growth was inhibited to a greater degree in mice treated by intratumoral injection of MGDG combined with irradiation as compared to either one alone (P < 0.05). This is the first report demonstrating that MGDG enhances the cytotoxicity of radiation to induce apoptosis of cancer cells in vitro and in vivo. Our findings indicate that this therapeutic combination can be an effective strategy for the treatment of pancreatic cancer.

Gold Nanoparticle-Incorporated Molecularly Imprinted Microgels as Radiation Sensitizers in Pancreatic Cancer

Abstract: Radiation therapy is a powerful approach for treating pancreatic cancer, a representative refractory cancer with a high fatality rate, and efforts have been made to decrease the radiation dose and suppress the side effects related to damage to normal tissues during radiation therapy. Gold nanoparticles (Au NPs) are known to possess radiosensitizing activity and low biotoxicity; however, Au NP-incorporated biomaterials have not been investigated as feasible radiosensitizers for use in vivo. Accordingly, in this study, Au NP-incorporated molecularly imprinted polymer microgels (Au-MIP microgels) were created as radiation sensitizers using a newly developed one-pot seeded precipitation polymerization method, and the radiation-sensitizing effects of the Au-MIP microgels were investigated in mice bearing pancreatic tumors. In mice injected with the Au-MIP microgels, tumor sizes were smaller than those in control mice injected with buffer solution when X-ray irradiation was performed. Furthermore, biotoxicity w...

Titanium Dioxide: From Engineering to Applications

Abstract: Titanium dioxide (TiO2) nanomaterials have garnered extensive scientific interest since 1972 and have been widely used in many areas, such as sustainable energy generation and the removal of environmental pollutants. Although TiO2 possesses the desired performance in utilizing ultraviolet light, its overall solar activity is still very limited because of a wide bandgap (3.0–3.2 eV) that cannot make use of visible light or light of longer wavelength. This phenomenon is a deficiency for TiO2 with respect to its potential application in visible light photocatalysis and photoelectrochemical devices, as well as photovoltaics and sensors. The high overpotential, sluggish migration, and rapid recombination of photogenerated electron/hole pairs are crucial factors that restrict further application of TiO2. Recently, a broad range of research efforts has been devoted to enhancing the optical and electrical properties of TiO2, resulting in improved photocatalytic activity. This review mainly outlines state-of-the-art modification strategies in optimizing the photocatalytic performance of TiO2, including the introduction of intrinsic defects and foreign species into the TiO2 lattice, morphology and crystal facet control, and the development of unique mesocrystal structures. The band structures, electronic properties, and chemical features of the modified TiO2 nanomaterials are clarified in detail along with details regarding their photocatalytic performance and various applications.

Molecularly Imprinted Polymers: Antibody Mimics for Bioimaging and Therapy.

Abstract: Molecularly imprinted polymers (MIPs) are tailor-made chemical receptors that recognize and bind target molecules with a high affinity and selectivity. MIPs came into the spotlight in 1993 when they were dubbed "antibody mimics," and ever since, they have been widely studied for the extraction or trapping of chemical pollutants, in immunoassays, and for the design of sensors. Owing to novel synthesis strategies resulting in more biocompatible MIPs in the form of soluble nanogels, these synthetic antibodies have found favor in the biomedical domain since 2010, when for the first time, they were shown to capture and eliminate a toxin in live mice. This review, covering the years 2015-2020, will first describe the rationale behind these antibody mimics, and the different synthesis methods that have been employed for the preparation of MIPs destined for in vitro and in vivo targeting and bioimaging of cancer biomarkers, an emerging and fast-growing area of MIP applications. MIPs have been synthesized for targeting and visualizing glycans and protein-based cell receptors overexpressed in certain diseases, which are well-known biomarkers for example for tumors. When loaded with drugs, the MIPs could locally kill the tumor cells, making them efficient therapeutic agents. We will end the review by reporting how MIPs themselves can act as therapeutics by inhibiting cancer growth. These works mark a new opening in the use of MIPs for antibody therapy and even immunotherapy, as materials of the future in nanomedicine.

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells.

Abstract: Radiotherapy is one of the major therapeutic strategies for cancer treatment. In the past decade, there has been growing interest in using high Z (atomic number) elements (materials) as radiosensitizers. New strategies in nanomedicine could help to improve cancer diagnosis and therapy at cellular and molecular levels. Metal-based nanoparticles usually exhibit chemical inertness in cellular and subcellular systems and may play a role in radiosensitization and synergistic cell-killing effects for radiation therapy. This review summarizes the efficacy of metal-based NanoEnhancers against cancers in both in vitro and in vivo systems for a range of ionizing radiations including gamma-rays, X-rays, and charged particles. The potential of translating preclinical studies on metal-based nanoparticles-enhanced radiation therapy into clinical practice is also discussed using examples of several metal-based NanoEnhancers (such as CYT-6091, AGuIX, and NBTXR3). Also, a few general examples of theranostic multimetallic nanocomposites are presented, and the related biological mechanisms are discussed.

Health Concerns of Various Nanoparticles: A Review of Their in Vitro and in Vivo Toxicity.

Abstract: Nanoparticles (NPs) are currently used in diagnosis and treatment of many human diseases, including autoimmune diseases and cancer. However, cytotoxic effects of NPs on normal cells and living organs is a severe limiting factor that hinders their use in clinic. In addition, diversity of NPs and their physico-chemical properties, including particle size, shape, surface area, dispersity and protein corona effects are considered as key factors that have a crucial impact on their safe or toxicological behaviors. Current studies on toxic effects of NPs are aimed to identify the targets and mechanisms of their side effects, with a focus on elucidating the patterns of NP transport, accumulation, degradation, and elimination, in both in vitro and in vitro models. NPs can enter the body through inhalation, skin and digestive routes. Consequently, there is a need for reliable information about effects of NPs on various organs in order to reveal their efficacy and impact on health. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.