Papers - Komatsu Syuuhei
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Preparation of thermoresponsive core-corona particles for controlled phagocytosis via surface properties and particle shape transformation Invited Reviewed International journal
Syuuhei Komatsu, Takuma Suzuki, Yota Kosukegawa, Masatoshi Kawase, Takuya Matsuyama, Taka-Aki Asoh, Akihiko Kikuchi
Journal of Controlled Release 381 113652 - 113652 2025.03
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
Cell-particle interactions, such as phagocytosis, exhibit variability based on particle shape, surface physical properties, and diameter. These interactions can be intentionally modified through in situ change in the physical characteristics of the particulate materials. By manipulating both the surface properties and shape of the particles, it may be feasible to regulate their interactions with cells. Objective of this research is to prepare thermoresponsive core-corona particles those undergo transformation and alteration in surface solubility near physiological temperature and to investigate particle shape- and surface physical property-dependent phagocytosis. The glass transition temperature of the prepared particles was controlled via the composition of the polymer core. Rod-type particles, prepared by uniaxially stretching particle-containing films at above the glass transition temperature of the core-forming materials, demonstrated reduced phagocytosis by macrophages compared to that of spherical particles. Furthermore, the physical properties of the particle surface exerted a significant influence on phagocytosis, with hydrophobic particles being more readily engulfed. Consequently, precise control of phagocytosis can be controlled by manipulating the particle's shape and surface properties. The prepared particles have potential applications as drug delivery system carriers, enabling the regulation of cell interactions via particle shape and surface physical properties induced by temperature changes.
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Thermoresponsive degradable hydrogels with renewable surfaces for protein removal Reviewed International journal
Syuuhei Komatsu, Naoki Kamei, Akihiko Kikuchi
Biomaterials Science 13 ( 1 ) 324 - 329 2025.01
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Royal Society of Chemistry (RSC)
In this paper, the synthesis of a thermoresponsive degradable gel that can effectively remove proteins by surface degradation was reported. The thermoresponsive shrinkage behavior caused decomposition near the surface, effectively removing proteins.
DOI： 10.1039/d4bm01383b
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In silico model to predict dermal absorption of chemicals in finite dose conditions. Reviewed
Ibuki Narita, Hiroaki Todo, Chihiro Fujiwara, Hiroyuki Teramae, Takeshi Oshizaka, Shoko Itakura, Syuuhei Komatsu, Kozo Takayama, Kenji Sugibayashi
The Journal of toxicological sciences 50 ( 4 ) 171 - 186 2025
Language：English Publishing type：Research paper (scientific journal)
The development of in silico approaches that can estimate the dermal absorption of chemicals exposed in practical conditions is highly anticipated. In the present study, an in silico model to estimate both the dermal absorption rate and dermal permeation profile was developed for the application of chemicals in finite dose conditions. Forty-three chemicals with molecular weights in the range 116-362 and logKo/w in the range 1.1-4.5 were used to develop an in silico model. A gradient boosting tree approach was applied to estimate permeation parameters for diffusion and partition coefficients of the chemicals in skin using physicochemical parameters of the chemicals such as molecular weight, lipophilicity, and the highest and lowest occupied molecular orbitals as the descriptor. In addition, 11 chemicals with different molecular weights and lipophilicities were applied on excised human skin in a finite dose condition, and dermal absorption profiles were obtained. Consideration of donor-solvent evaporation time, saturated concentrations of the chemicals, and donor-solvent coverage area on the skin surface, in addition to estimated skin permeation parameters of the chemicals, showed comparatively good dermal absorption profiles, although some cases of underestimation of dermal absorption were identified. It will be necessary to verify the accuracy of this model through experiments using more chemicals. However, the obtained results suggested that the established model may be valid to estimate the dermal absorption of chemicals in practical conditions.
DOI： 10.2131/jts.50.171
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Effect of the barrier function of stratum corneum and viable epidermis and dermis on the skin concentration of topically applied chemicals. Reviewed
Hiroaki Todo, Takeshi Oshizaka, Syuuhei Komatsu, Kenji Sugibayashi
The Journal of toxicological sciences 50 ( 4 ) 187 - 198 2025
Language：English Publishing type：Research paper (scientific journal)
Three-dimensional cultured skin (3D skin) models have been utilized for in vitro skin permeation tests to evaluate the skin permeation rate and local effects (efficacy and toxicity) of applied chemicals, particularly from the perspective of the 3Rs (reduction, replacement, refinement) approach. The steady-state concentration of applied chemicals at different depths in the viable epidermis and dermis (VED) is affected by their skin permeation parameters, such as permeability coefficient (Kp) and partition coefficient (K) from the donor solution to the skin of the chemicals. In the present study, the steady-state concentration of chemicals in the VED of EpiDerm 606X (EpiDerm) as representative of a 3D skin model were compared with hairless rat skin. The VED concentrations of chemicals in EpiDerm were higher than those in hairless rat skin when a model hydrophilic compound, antipyrine, and a model lipophilic compound, flurbiprofen, were applied, suggesting that the barrier functions of the VED against the whole skin were higher in EpiDerm than in hairless rat skin. When an ester compound, ethyl nicotinate, was applied, the VED concentration of nicotinic acid, a metabolite of ethyl nicotinate, was lower in EpiDerm than in hairless rat skin. These differences in the VED concentrations of applied chemicals might be related to false-positives and -negatives of topical effects evaluated with 3D skin models. It is important to pay particular attention to differences in VED concentration in 3D skin models and real skin when evaluating local efficacy and toxicity using 3D skin models.
DOI： 10.2131/jts.50.187
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Plasmid DNA Delivery into the Skin via Electroporation with a Depot-Type Electrode Reviewed International journal
Yuya Yoshida, Manami Aoki, Kalin Nagase, Koichi Marubashi, Hiroyuki Kojima, Shoko Itakura, Syuuhei Komatsu, Kenji Sugibayashi, Hiroaki Todo
Pharmaceutics 16 ( 9 ) 1219 - 1219 2024.09
Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG
Objectives: Non-viral mediated plasmid DNA transfection by electroporation (EP) is an established method for gene transfection. In this study, the usefulness of direct EP at an intradermal (i.d.) site (DEP) with implanted electrodes to achieve a high protein expression level was investigated. In addition, DEP application with various intervals with a low application voltage was also evaluated to confirm its effect on protein expression. Methods: Green fluorescent protein (GFP)- and luciferase-encoding DNA were administrated, and GFP and luciferase were evaluated. Results: A higher protein expression level was observed after green fluorescent protein (GFP)- and luciferase-encoding DNA were delivered by i.d. injection followed by DEP application. When luciferase expression was observed with an in vivo imaging system, continuous expression was confirmed over 21 days after i.d. injection followed by DEP at 100 V. This approach provided increased gene expression levels compared with conventional EP methods via the stratum corneum layer. In addition, the effect of application voltage on luciferase expression was investigated; two-time applications (repeated DEP) at 20 V with 5 min intervals showed similar luciferase expression level to single DEP application with 100 V. Histological observations showed the skin became thicker after a single DEP at 100 V, whereas no apparent thickness changes were confirmed after repeated DEP at 20 V with 5 min intervals. Conclusions: This study revealed that direct i.d. voltage application achieved high protein expression levels even at low voltages. Skin is a promising administration site for DNA vaccines, so this approach may be effective for DNA vaccine delivery into skin tissue.
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Formation mechanism of anisotropic gelatin hydrogel by self-assembly on oriented templates Invited Reviewed
Kohei Kawaguchi, Tamaki Maeda, Syuuhei Komatsu, Yoshihiro Nomura, Kazuki Murai
Molecular Systems Design & Engineering 9 ( 6 ) 561 - 570 2024.06
Language：English Publishing type：Research paper (scientific journal) Publisher：Royal Society of Chemistry (RSC)
The development of structurally controlled techniques inspired by the structural formation of living systems is of great importance for the fabrication of next-generation functional soft materials using environmentally friendly processes.
DOI： 10.1039/d4me00023d
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Preparation of Degradable and Transformable Core–Corona-Type Particles that Control Cellular Uptake by Thermal Shape Change Reviewed International journal
Syuuhei Komatsu, Satoshi Yamada, Akihiko Kikuchi
ACS Biomaterials Science & Engineering 10 ( 2 ) 897 - 904 2024.01
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：American Chemical Society (ACS)
Particle-cell interactions, such as cellular uptake, vary depending on the particle size, shape, and surface properties. By dynamic control of the physical properties of particles, microparticle-cell interactions can intentionally be altered. Particle degradability is also necessary for their application in the body. In this study, we aimed to prepare degradable core-corona-type particles that are deformed near the body temperature and investigated particle shape-dependent cellular uptake. Degradable and transformable particles consisting of poly(2-methylene-1,3-dioxepane)-co-poly(ethylene glycol) with three-armed poly(ε-caprolactone) (PCL) were prepared. The particle melting point was controlled by the chain length of the three-armed PCL. Particle degradation occurred under both acidic and alkaline conditions via ester group hydrolysis in the polymer backbones. The rod-shaped microparticles prepared by uniaxial stretching at a temperature above the melting point of the core showed less uptake into macrophages than did the spherical microparticles. Therefore, the degradable transformable particles enable macrophage interaction control via stimuli-regulated particle shapes and are expected to be applied as drug delivery carriers that can be decomposed and excreted from the body.
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The Design of Thermoresponsive Polymeric Particles Invited Reviewed
Syuuhei KOMATSU, Akihiko KIKUCHI
Journal of the Japan Society of Colour Material 96 ( 10 ) 338 - 343 2023.10
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Society of Colour Material
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A Simple Colorimetric Assay of Bleomycin‐Mediated DNA Cleavage Utilizing Double‐Stranded DNA‐Modified Gold Nanoparticles Reviewed International journal
Yoshitsugu Akiyama, Kazunori Kimura, Syuuhei Komatsu, Tohru Takarada, Mizuo Maeda, Akihiko Kikuchi
ChemBioChem 24 ( 1 ) e202200451 2022.09
Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley
A colorimetric assay of DNA cleavage by bleomycin (BLM) derivatives was developed utilizing high colloidal stability on double-stranded (ds) DNA-modified gold nanoparticles (dsDNA-AuNPs) possessing a cleavage site. The assay was performed using dsDNA-AuNPs treated with inactive BLM or activated BLM (Fe(II)⋅BLM). A 10-min exposure in dsDNA-AuNPs with inactive BLM treatment resulted in a rapid color change from red to purple because of salt-induced non-crosslinking aggregation of dsDNA-AuNPs. In contrast, the addition of active Fe(II)⋅BLM retained the red color, probably because of the formation of protruding structures at the outermost phase of dsDNA-AuNPs caused by BLM-mediated DNA cleavage. Furthermore, the results of our model experiments indicate that oxidative base release and DNA-cleavage pathways could be visually distinguished with color change. The present methodology was also applicable to model screening assays using several drugs with different mechanisms related to antitumor activity. These results strongly suggest that this assay with a rapid color change could lead to simple and efficient screening of potent antitumor agents.
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Degradation and drug release profile of degradable core-corona type particles under acidic condition for cancer treatment Reviewed International journal
Syuuhei Komatsu, Satomi Ishida, Taka-Aki Asoh, Akihiko Kikuchi
Reactive and Functional Polymers 177 105321 - 105321 2022.08
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
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Preparation of carbonate apatite capsules based on degradable polymer-based coacervates and their osteoinductive effect on osteoblasts Reviewed
Syuuhei Komatsu, Taka-Aki Asoh, Akihiko Kikuchi
IUMRS-ICYRAM2022 2022.08
Authorship：Lead author Language：English
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Facile fabrication of gelatin hydrogels with anisotropic gel properties via self-assembly Reviewed International journal
Kohei Kawaguchi, Syuuhei Komatsu, Akihiko Kikuchi, Yoshihiro Nomura, Kazuki Murai
Polymer Journal 54 ( 3 ) 377 - 383 2022.03
Language：English Publishing type：Research paper (scientific journal)
Using a facile method, a gelatin hydrogel with anisotropic gel properties was prepared on a substrate via hydrogelation to induce self-assembly. The specific structure of the gelatin network of the hydrogel was controlled by changing the specific surface properties of the substrate. The anisotropic swelling and mechanical behavior of the hydrogel were found to be based on its specific structure.
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Protein Removal from Hydrogels through Repetitive Surface Degradation Reviewed International journal
Tatsuki Kamiya, Syuuhei Komatsu, Akihiko Kikuchi
ACS Applied Bio Materials 4 ( 12 ) 8498 - 8502 2021.12
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：American Chemical Society (ACS)
Suppression of protein adsorption is a necessary property for materials used in the living body. In this study, thermoresponsive and degradable hydrogels were prepared by the radical polymerization of 2-methylene-1,3-dioxepane, 2-hydroxyethyl acrylate (HEA), and poly(ethylene glycol) monomethacrylate (PEGMA). The prepared hydrogels re-exposed PEG-grafted chains to the interface through surface degradation, which was confirmed by the maintenance of the chemical composition of the hydrogel surfaces after hydrolysis. Notably, adsorbed proteins can be removed from the hydrogel surfaces through hydrogel surface degradation at least thrice.
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Material Design of Drug Loadable Scaffold for Bone Regeneration and Treatment Invited Reviewed
Syuuhei Komatsu, Akihiko Kikuchi
28 290 - 294 2021.09
Authorship：Lead author Language：Japanese Publishing type：Part of collection (book)
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Facile preparation of multi-stimuli-responsive degradable hydrogels for protein loading and release. Reviewed International journal
Syuuhei Komatsu, Moeno Tago, Yu Ando, Taka-Aki Asoh, Akihiko Kikuchi
Journal of controlled release : official journal of the Controlled Release Society 331 1 - 6 2021.03
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
Functional materials that can recognize the tumor microenvironment, characterized by acidic or reducing conditions, are needed for the designing of drug delivery carriers for cancer treatment. Hydrogels are potential protein drug carriers because they contain a large amount of water and stimuli-responsive functions can easily be introduced in them. However, it is difficult to introduce multi-stimuli-responsive functions and degradability at the same time. Here, we synthesized thermo- and pH-responsive hydrogels via a coupling reaction between poly(ethylene glycol) diglycidyl ether (PEGDE) and cystamine (CA). The prepared hydrogels showed lower critical solution temperature-type thermoresponsive behavior and pH-responsive swelling changes due to the protonation of secondary and/or tertiary amino groups arising from the crosslinking agent CA. Under reducing conditions, the hydrogels were degraded via the thiol exchange reaction in the presence of dithiothreitol or glutathione. The loading and release properties of FITC-labeled model proteins from the hydrogels were investigated. The loaded amount of the protein increased with decreasing molecular weight or hydrodynamic radius, which is based on the size of the network structure of the hydrogels. Notably, loaded proteins in the hydrogels were released only under reducing conditions, which mimic the tumor microenvironment. Thus, the prepared multi-responsive degradable hydrogels are expected to be used as functional drug delivery carriers for cancer treatment.
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Facile preparation of 2-methylene-1, 3-dioxepane-based thermoresponsive polymers and hydrogels Reviewed International journal
Syuuhei Komatsu, Takuya Sato, Akihiko Kikuchi
POLYMER JOURNAL 53 ( 6 ) 731 - 739 2021.02
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
Thermoresponsive and degradable hydrogels are considered promising materials for the development of smart drug delivery carriers that can be applied in the human body. However, the synthesis of a thermoresponsive degradable hydrogel with desirable properties is challenging. Here, we prepared thermoresponsive degradable copolymers and hydrogels by radical copolymerization of 2-methylene-1,3-dioxepane and N,N-dimethylacrylamide. The obtained polymers exhibited low critical solution temperature-type phase separation and a swelling-deswelling behavior. Under alkaline conditions (pH 11.3), these materials degraded and turned into water-soluble oligomers. In addition, the hydrogels self-degraded in PBS due to the decreased pH of the inner hydrogel. The prepared thermoresponsive degradable polymers and hydrogels have potential applicability as stimuli-responsive drug delivery carriers and cell culture scaffolds.
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Development of carbonate apatite capsules based on degradable coacervate droplets for bone defect treatment Invited Reviewed
Syuuhei Komatsu
Drug Delivery System 36 ( 3 ) 216 - 217 2021
Authorship：Lead author Publishing type：Research paper (scientific journal)
DOI： 10.2745/dds.36.216
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Organic-inorganic Hybrid Drug loadable Carbonate Apatite Capsules for Bone Tissue Engineering Reviewed
Syuuhei Komatsu, Shuhei Abe, Taka-Aki Asoh, Akihiko Kikuchi
11th World Biomaterial Congress 2020.12
Authorship：Lead author Language：English
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骨欠損再生のための足場材料の展開 Reviewed
小松周平、安部秀平、菊池明彦
BIOClinica 35 ( 7 ) 68 - 72 2020.06
Authorship：Lead author Language：Japanese
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Preparation of thermoresponsive nanoparticles exhibiting biomolecule recognition ability via atom transfer radical dispersion polymerization. Reviewed International journal
Takuya Matsuyama, Hiroyuki Hayashi, Syuuhei Komatsu, Taka-Aki Asoh, Akihiko Kikuchi
Colloids and surfaces. B, Biointerfaces 183 110370 - 110370 2019.11
Language：English Publishing type：Research paper (scientific journal)
Thermoresponsive core-corona type nanoparticles were prepared exhibiting biomolecule recognition ability on their surfaces. These thermoresponsive nanoparticles were prepared from a poly(N-isopropylacrylamide) (PNIPAAm) macro-initiator and styrene (St) in a polar solvent via atom transfer radical dispersion polymerization. The PNIPAAm macro-initiator contains an alkyl halide and/or phthalimide group on the terminated group of the polymer chain, and thus, the grafting of PNIPAAm on the PSt core resulted in terminating phthalimide end groups. These terminal groups were utilized to immobilize biomolecule recognition units, and the dispersion stabilities of the nanoparticles were found to change in aqueous solution at room temperature due to alteration of the terminating PNIPAAm groups by the presence of biomolecules at different concentrations.