Atsushi Kimura

Preclinical drug testing in animals is costly, raises ethical concerns, and often fails to predict human responses, highlighting the need for alternatives. Microphysiological systems (MPSs) have emerged as alternatives to animal experiments in physiology and drug development. However, conventional MPSs are designed for specific applications and lack versatility and scalability, limiting broader adoption. In this study, we developed a “Buildable and Linkable Organ on a Chip” (BLOC) that enables flexible construction of diverse MPS configurations. In this system, Culture, Control, and Analysis BLOCs have been standardized to the same size and linked using inlet/outlet joints for perfusion. Radiation‐induced chemical reactions are used to suppress the adsorption and absorption of small hydrophobic molecules by BLOCs composed of polydimethylsiloxane. BLOCs for 2D/3D culture can also encapsulate radiation‐crosslinked protein hydrogels with designed stiffness and microtopography to mimic the microenvironment in vivo. A perfusion device connecting Culture BLOCs is designed for a toxicity assay mimicking systemic circulation using six types of organoids. An automatic enzyme‐linked immunosorbent assay device connecting Culture, Control, and Analysis BLOCs detects proteins released from organoids. BLOCs, which users can freely configure to suit their needs, are expected to emerge as powerful tools in basic research and preclinical trials using MPSs.

Nano-theranostics using biodegradable polymers are effective for the diagnosis and treatment of intractable cancers; however, there is a need for technology that controls bioavailability and biodegradability without compromising biocompatibility. In this study, peptide nanoparticles (NPs) with controlled particle size and biodegradability were prepared by ionizing radiation and loaded with imaging agents and anticancer drugs to develop novel nano-theranostics for pancreatic cancer diagnosis and treatment. Peptides composed of histidine, glycine, glutamic acid, and an arginine-glycine-aspartic acid motif were synthesized by the solid-phase synthesis method. Their aqueous solutions were irradiated with γ-rays to produce NPs with a particle size of less than 50 nm, enabling penetration of the pancreatic cancer stroma. The radiation crosslinking of peptides, with or without the arginine-glycine-aspartic acid motif, in water was investigated by pulse radiolysis. Peptide NPs loaded with fluorescent labeling or magnetic resonance imaging agents were efficiently taken up by pancreatic cancer cells. Cisplatin-loaded peptide NPs produced by higher-dose irradiation suppress drug-release rates owing to their lower biodegradability. In conclusion, peptide NPs with controllable particle size and biodegradability were produced by ionizing radiation and loaded with fluorescent labeling agents, magnetic resonance imaging agents, and anticancer drugs to develop a new nano-theranostics drug for pancreatic cancer diagnosis and treatment.

Microphysiological systems (MPSs) are attractive alternatives to animal experiments in physiology, pathophysiology, and drug development. However, conventional MPSs are designed for specific applications and have low versatility and scalability. Here, we developed a “Buildable and Linkable Organ on a Chip” (BLOC) to construct diverse MPSs. The Culture, Control, and Analysis BLOCs were standardized to the same size and linked using inlet/outlet joints for perfusion. Radiation-induced chemical reactions were used to suppress the adsorption and absorption of small hydrophobic molecules by BLOCs composed of polydimethylsiloxane. BLOCs for 2D/3D culture could also encapsulate radiation-crosslinked protein hydrogels with designed stiffness and microtopography to mimic the microenvironment in vivo . A perfusion device connecting Culture BLOCs was designed for a toxicity assay mimicking the systemic circulation using six types of organoids. An automatic enzyme-linked immunosorbent assay device connecting Culture, Control, and Analysis BLOCs detected proteins released from organoids. BLOCs, which users can freely configure to suit their needs, is expected to become powerful tools in basic research and preclinical trials using MPSs.

Pancreatic cancer remains difficult to diagnose using currently available imaging probes. Thus, this study aimed to develop a novel imaging agent for the diagnosis of pancreatic cancer using positron emission tomography (PET). Specifically, this study explores gelatin-based nanoparticles fabricated via radiation-induced crosslinking, as gelatin is known for its ability to produce biocompatible materials. Aqueous gelatin solutions were irradiated with γ-rays to produce nanoparticles with average diameters of 5–20 nm via a radiation crosslinking technique. The gelatin nanoparticles were labeled with ⁶⁴Cu, exhibiting negative surface potentials. Furthermore, the nanoparticles were evaluated in vivo by injecting them into pancreatic tumor-bearing mice. Notably, the nanoparticles accumulated in the tumors. Hence, ⁶⁴Cu-labeled gelatin nanoparticles show promise as a platform for next-generation PET imaging agents for pancreatic cancer.

Pulse radiolysis was employed to investigate fundamental radiation chemical reactions, which are essential in the radiation protection of DNA. Two positively charged peptides (PCPs), histidine-tyrosine-histidine (His-Tyr-His) and lysine-tyrosine-lysine (Lys-Tyr-Lys), as well as the amino acids that constitute them, were involved. The reaction rate constants for tyrosine (Tyr), histidine (His), lysine (Lys), His-Tyr-His, and Lys-Tyr-Lys with OH radicals (^•OH) were (1.6 ± 0.3) × 10¹⁰, (9.0 ± 0.9) × 10⁹, (1.4 ± 0.3) × 10⁹, (1.8 ± 0.1) × 10¹⁰, and (1.0 ± 0.1) × 10¹⁰ M^-1s^-1, respectively, indicating that formation of peptide bond can affect the reaction of amino acids with ^•OH. Observed transient absorption spectra indicated a shielding effect of the His or Lys residues at both ends of the PCPs on the centrally located Tyr. The measurement of chemical repair capabilities using deoxyguanosine monophosphate (dGMP) as a model for DNA demonstrated that the reaction rate constants of Tyr, His-Tyr-His, and Lys-Tyr-Lys with dGMP radicals were (2.2 ± 0.5) × 10⁸, (2.3 ± 0.1) × 10⁸, and (3.3 ± 0.4) × 10⁸ M^-1s^-1, respectively, implying that the presence of a positive charge may enhance the chemical repair process.

We present a crop classification method that uses L-band synthetic aperture radar (SAR) data from PALSAR-2 and C-band SAR data from RADARSAT-2, employing random forests as a classification algorithm, and evaluate it from the perspectives of accuracy. It was calculated that backscatter coefficient (HH, HV and VV) and polarimetric parameters (double bounce, volume scattering, surface scattering, entropy, anisotropy and alpha angle) from RADARSAT-2 and PALSAR-2 quad-polarimetric data. The HH backscatter coefficient was calculated from PALSAR-2 single-polarimetric data. Classification using data from one scene gave better overall accuracy for the RADARSAT-2 quad-polarimetric data than for the PALSAR-2 quad-polarimetric data. For classification using one scene from RADARSAT-2 and one from PALSAR-2, the accuracy was higher than that using only one RADARSAT-2 scene, and the difference was statistically significant. When using data from one scene, it is useful to use both C-band and L-band data. Classification using data from three scenes gave better overall accuracy for the RADARSAT-2 data than for the PALSAR-2 data. However, there was no significant difference in classification between combining three scenes from each of the satellites and using three scenes from only RADARSAT-2. When using data from multiple scenes, only C-band data can be gave sufficient accuracy. However, when using single-polarimetric data, it is not possible to calculate valid variables for classification. Therefore, it is necessary to examine the accuracy of classification using quad-polarimetric data of PALSAR-2.

Nanoparticle-based drug delivery systems (DDS) have been developed as effective diagnostic and low-dose imaging agents. Nano-imaging agents with particles greater than 100 nm are difficult to accumulate in pancreatic cancer cells, making high-intensity imaging of pancreatic cancer challenging. Peptides composed of histidine and glycine were designed and synthesized. Additionally, aqueous peptide solutions were irradiated with γ-rays to produce peptide nanogels with an average size of 25–53 nm. The mechanisms underlying radiation-mediated peptide crosslinking were investigated by simulating peptide particle formation based on rate constants. The rate constants for reactions between peptides and reactive species produced by water radiolysis were measured using pulse radiolysis. HGGGHGGGH (H9, H—histidine; G—glycine) particles exhibited a smaller size, as well as high formation yield, stability, and biodegradability. These particles were labeled with fluorescent dye to change their negative surface potential and enhance their accumulation in pancreatic cancer cells. Fluorescent-labeled H9 particles accumulated in PANC1 human pancreatic cancer cells, demonstrating that these particles are effective nano-imaging agents for intractable cancers.

The elasticity, topography, and chemical composition of cell culture substrates influence cell behavior. However, the cellular responses to in vivo extracellular matrix (ECM), a hydrogel of proteins (mainly collagen) and polysaccharides, remain unknown as there is no substrate that preserves the key features of native ECM. This study introduces novel collagen hydrogels that can combine elasticity, topography, and composition and reproduce the correlation between collagen concentration ( C ) and elastic modulus ( E ) in native ECM. A simple reagent-free method based on radiation-cross-linking altered ECM-derived collagen I and hydrolyzed collagen (gelatin or collagen peptide) solutions into hydrogels with tunable elastic moduli covering a broad range of soft tissues ( E = 1–236 kPa) originating from the final collagen density in the hydrogels ( C = 0.3%–14%) and precise microtopographies (⩾1 μm). The amino acid composition ratio was almost unchanged by this method, and the obtained collagen hydrogels maintained enzyme-mediated degradability. These collagen hydrogels enabled investigation of the responses of cell lines (fibroblasts, epithelial cells, and myoblasts) and primary cells (rat cardiomyocytes) to soft topographic cues such as those in vivo under the positive correlation between C and E . These cells adhered directly to the collagen hydrogels and chose to stay atop or spontaneously migrate into them depending on E , that is, the density of the collagen network, C . We revealed that the cell morphology and actin cytoskeleton organization conformed to the topographic cues, even when they are as soft as in vivo ECM. The stiffer microgrooves on collagen hydrogels aligned cells more effectively, except HeLa cells that underwent drastic changes in cell morphology. These collagen hydrogels may not only reduce in vivo and in vitro cell behavioral disparity but also facilitate artificial ECM design to control cell function and fate for applications in tissue engineering and regenerative medicine.

An artificial organ based on polyvinyl alcohol (PVA) hydrogel was developed to train medical staff to improve their ablation therapy skills, by using the radiation cross‐linking technique. The aqueous PVA solution was irradiated with γ‐rays or electron beams to produce a highly transparent, high‐strength, and flexible crosslinked hydrogel without using a crosslinking agent. Physical properties of the hydrogel, such as, gel fraction, swelling, and elastic modulus, were controlled by changing the radiation dose. The catheter ablation region on the surface of the cardiac phantom produced from PVA hydrogel with temperature‐responsive pigment inks can be visually identified by the color change. The tumor organ phantom consists of the PVA hydrogel with the purple pigment ink (healthy organ site) and red PVA hydrogel with cellulose (the tumor sites) was developed by applying this radiation crosslinking technique. The positions of the tumor hydrogel and the ablation electrode needle can be confirmed through ultrasound echography. It is possible to practice ablation on the tumor site while observing the echo images under conditions similar to the actual treatment. These novel human organ phantoms are created as a means for ablation training for treating cardiac arrhythmia and liver cancer using the radiation crosslinking technology.