Papers - INADA Asuka
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Water‐Based Synthesis of β‐Sheet‐Like Supramolecular Metallohydrogel Organized by Using a Native Ultrashort Peptide Sequence Reviewed International journal
Asuka Inada, Aki Motomura, Tatsuya Oshima
Chemistry – A European Journal 30 ( 11 ) e202303160 2024.2
Authorship：Lead author, Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley
Designing supramolecular hydrogels using short peptides is challenging. To control self‐assembly, a certain amount of organic solvent is typically added to the system, or the short peptide is modified with a functional group that is hydrophobic, hydrophilic, or highly coordinative. We discovered that l‐His‐l‐Ile‐l‐Thr (HIT), a very short unmodified “native” tripeptide, selectively responds to Cu2+ ions in pure water to form a transparent supramolecular metallohydrogel. Circular dichroism analysis revealed that Cu2+ ions, but no other metal species, caused HIT to change from a random‐coil‐like to a β‐sheet‐like structure. Other spectroscopic methods were used to characterize the properties of the supramolecular metallohydrogel. These results are expected to facilitate the development of native short peptides as advanced functional biomaterials.
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Controlled release of nanoparticles in the tumor environment by tripeptide coordination-driven self-assembly Reviewed International journal
Inada A., Hoshihara N., Oshima T.
Colloids and Surfaces A Physicochemical and Engineering Aspects 723 2025.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Colloids and Surfaces A Physicochemical and Engineering Aspects
In this study, nanoparticles (NPs) were synthesized by the coordination-bond-driven self-assembly of two tripeptides, H-Trp-His-Phe-OH (WHF) and H-Trp-His-Tyr-OH (WHY), with zinc ions. In addition, a one-pot method was developed to synthesize NP complexes with the anticancer drug doxorubicin (DOX) for application as drug delivery carriers. DOX release from DOX@NP-Zn(WHF) and DOX@NP-Zn(WHY) was enhanced under pH conditions mimicking the tumor microenvironment compared to physiological conditions. Cell viability assays demonstrated that NP-Zn(WHF) and NP-Zn(WHY) carriers exhibited minimal toxicity, whereas DOX@NP-Zn(WHF) and DOX@NP-Zn(WHY) showed excellent anticancer activity against tumor cells in a DOX concentration-dependent manner. NP-Zn(WH-X) could be a promising new carrier for controlled drug delivery in cancer therapy.
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Machine Learning Prediction of Au(III) Extractability of Various Organic Solvents Based on Ion Solvation in Hydrochloric Acid Media Reviewed International journal
Oshima T., Iwakiri Y., Yokota H., Inada A.
ACS Sustainable Chemistry and Engineering 13 ( 24 ) 9110 - 9118 2025.6
Language：English Publishing type：Research paper (scientific journal) Publisher：ACS Sustainable Chemistry and Engineering
Selective recovery of gold from waste electrical and electronic equipment has attracted increasing attention. Au(III), which is present as tetrachloroauric acid (HAuCl<inf>4</inf>) in hydrochloric acid media, can be extracted by using various organic solvents, such as ketones and ethers. However, the decisive factors of the solvent for predicting Au(III) extractability have not been confirmed. In the present study, the relationship between the extraction percentage of Au(III) and the properties of the solvent was investigated for 79 types of solvents. Based on the relationships between the Hansen solubility parameters of the solvent and the extraction percentage of Au(III) in 5.0 M HCl with a threshold of 80%, the extractability was classified with 93.7% accuracy. To predict the Au(III) extractability, a machine learning model was constructed using the relationship between the molecular descriptors of the solvents obtained from RDKit as explanatory variables and the extraction percentage of Au(III) as the objective variable. By selection of the descriptors that showed a strong correlation with the Au(III) extraction percentage, the squared correlation coefficient (R<sup>2</sup>) of the test data for the nonlinear support vector regression model using 35 descriptors was 0.943. Machine learning was performed again with the addition of surface charge density descriptors obtained from the solvent structure using the conductor-like screening model for real solvents. The R<sup>2</sup> value of the test data for the nonlinear support vector regression model using 28 descriptors, including the hydrogen bond acceptor descriptor as an additional descriptor, was 0.899, which was slightly lower than that of the model with 35 descriptors. Experimental validation using six additional solvents confirmed the model’s accuracy, with predicted values closely matching the measured extraction percentages.
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Sequence optimization of lipid-modified amphiphilic tetrapeptides as anticancer drug carriers. Reviewed International journal
Inada A, Sawao A, Shinoda M, Oshima T
Journal of pharmaceutical sciences 114 ( 6 ) 103768 2025.3
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Pharmaceutical Sciences
In this study, 19 tetrapeptides, each consisting of four amino acid residues, were designed and modified with oleic acid to serve as amphiphilic dispersants for anticancer drug delivery. The lipid-modified peptides (Ole-pep) were evaluated for their ability to disperse paclitaxel (Ptx), a poorly water-soluble anticancer drug. The water dispersibility of Ptx was significantly increased when peptides with two or more positively or negatively charged functional groups were used as dispersants. One specific Ole-pep demonstrated a critical micelle concentration of 0.0682 × 10−3 mol/dm3, confirming its excellent amphiphilic properties and capacity to encapsulate Ptx. Cytotoxicity studies in HeLa cells, a cell line derived from human cervical cancer cells, confirmed that the complexes with Ptx were highly cytotoxic regardless of the peptide used. Additionally, the results suggested that certain peptides, particularly those with a high number of Lys residues, exhibited cytotoxicity on their own.
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Evaluation of Water Dispersibility and Cell Accumulation of β-Cryptoxanthin Formulations Prepared Using Membrane Emulsification Method Reviewed International journal
Taniguchi Arisa, Ochi Takahiro, Oshima Tatsuya, Inada Asuka, Akaki Takeshi, Yamamoto Kenji, Shimizu Masataka
KAGAKU KOGAKU RONBUNSHU 51 ( 1 ) 12 - 17 2025.1
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Society of Chemical Engineers, Japan
Various health functions have been reported for β-cryptoxanthin (BCX), which is abundantly contained in citrus fruits. As BCX is a poorly water-soluble and chemically unstable carotene, formulation techniques for increased dispersibility in digestive fluids and stability is desired to improve oral bioavailability. In this study, an O/W emulsion was prepared using an oil phase containing BCX extracted from tangerine juice residue and an aqueous phase containing sodium caseinate (CasNa) and sucrose fatty acid ester (L-1695). The emulsion was then subjected to membrane emulsification using a Shirasu porous glass (SPG) membrane with a uniform pore size. The resulting emulsion was of monodisperse particle size and was lyophilized to obtain a solid dispersion. For the solid dispersion, the water dispersibility and thermal stability of BCX were significantly improved, and the particle size was also monodisperse. In order to evaluate the oral bioavailability of BCX, cell membrane permeation and accumulation tests for the BCX formulation after pseudo-digestion were performed using Caco-2 cell monolayer membranes. Cell membrane permeation of BCX was not confirmed, however, the amount of BCX accumulated in Caco-2 cells was increased by the formulation.
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Extraction of Amino Acid Esters Using a Pillar[6]arene Carboxylic Acid Derivative as a Novel Acidic Macrocyclic Compound Reviewed International journal
IKUSHIMA Yu, OSHIMA Tatsuya, INADA Asuka
Solvent Extraction Research and Development, Japan 32 ( 2 ) 79 - 87 2025
Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Association of Solvent Extraction
Pillararenes are a series of novel macrocyclic compounds discovered in the 2000s. However, solvent extraction based on ion exchange using pillararene derivatives is currently limited. Recently, a pillar[6]arene hexaacetic acid derivative (OctP[6]CH<sub>2</sub>COOH) has been developed as a new acidic extractant. In this study, the extraction of amino acid esters using OctP[6]CH<sub>2</sub>COOH was investigated. The extraction of tryptophan methyl ester using OctP[6]CH<sub>2</sub>COOH was much greater than that using the 6-fold equivalent monomer analog. The extraction of more hydrophobic cationic guests was relatively high. This process is based on a proton exchange reaction. The results of slope analysis and Job plot analysis confirmed the formation of a 1:1 complex between OctP[6]CH<sub>2</sub>COOH and the guest cation.
DOI： 10.15261/serdj.32.79
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Separation of gallium(III) using 2-nonanone based on ion solvation in acidic chloride media Reviewed International journal
Mai Hashizume, Tatsuya Oshima, Asuka Inada
Separation and Purification Technology 335 126156 - 126156 2024.5
Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
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A Comparative Study of Extraction of Selenium(IV) Using Various Organic Solvents in Hydrochloric Acid Media Reviewed International journal
Tatsuya OSHIMA, Mai HASHIZUME, Naoki MATSUO, Yuki KAWAGUCHI, Kaoru OHE, Asuka INADA
Solvent Extraction Research and Development, Japan 31 ( 2 ) 41 - 48 2024
Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Association of Solvent Extraction
To date, suitable organic solvents for the extraction of tetravalent selenium (Se(IV)) in highly concentrated hydrochloric acid have not been clarified systematically. In this study, the extraction of Se(IV) using various organic solvents was compared. Se(IV) was extracted from 8.0 mol/dm<sup>3</sup> hydrochloric acid using various ketones. Se(IV) extraction using ethers was lower, while that using hydrocarbons was negligible. The correlation between the extraction and log<i>P</i> value of solvents was small, however, the extraction using a hydrophobic dicyclohexyl ketone was lower. The extractability of Se(IV) by most solvents can be classified with the Hansen solubility parameters of the solvents. However, Se(IV) extracted by 2-nonanone was not stripped by contact with fresh aqueous solutions containing HCl, HNO<sub>3</sub>, NaOH, or EDTA.
DOI： 10.15261/serdj.31.41
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消化ペプチドとの複合化によるβ-クリプトキサンチンの水分散性およびCaco-2細胞膜透過性の改善 Reviewed
稲田飛鳥，野崎唯那，澤尾綾音，大島達也
化学工学論文集 2023.8
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal)
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Development of solvents for Au(III) extraction in hydrochloric acid media based on ion solvation with reference to the Hansen solubility parameters: Success of dicyclohexylketone Reviewed International journal
Tatsuya Oshima, Yuhi Iwakiri, Asuka Inada
Hydrometallurgy 220 106106 - 106106 2023.6
Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
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Extraction of Au(III) Using Aromatic Ketones in Acidic Chloride Media Reviewed
OSHIMA Tatsuya, MIYAKE Kota, HASHIZUME Mai, INADA Asuka
Solvent Extraction Research and Development, Japan 30 ( 2 ) 129 - 136 2023
Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Association of Solvent Extraction
Recently, the extraction of Au(III) using the series of aliphatic ketones in hydrochloric acid media has been investigated in detail. The present study describes the extraction behaviors of Au(III) using a series of aromatic ketones, which has never been reported. Aromatic ketones with shorter alkyl side chains showed higher extractability. The rapid extraction and the extraction capacity using aromatic ketones were comparable to the industrial extractant dibutyl carbitol (DBC). Aromatic ketones, except acetophenone, are less soluble in water than DBC. The flash points of aromatic ketones are satisfactorily high for industrial operation, but their specific gravities comparable to that of water are unwelcome. Butyrophenone selectively extracted Au(III) from many other metals, except for high extraction of Fe(III) and Ga(III) at high concentrations. Au(III) extracted using butyrophenone recovered quantitatively as metallic gold by reduction using oxalic acid.
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Development of Amphiphilic Short Peptides to Control Drug Inclusivity through Metal Complexation Reactions Reviewed International journal
Asuka Inada, Makoto Hitotsumatsu, Tatsuya Oshima
Journal of Chemical Engineering of Japan 56 ( 1 ) 2023
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Informa UK Limited
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Development of aromatic ethers as solvents for a calix[6]arene derivative and extraction of amino acids and proteins Reviewed International journal
Tatsuya Oshima, Tokiya Asano, Asuka Inada, Keisuke Ohto, Jumina
Journal of Inclusion Phenomena and Macrocyclic Chemistry 102 ( 5-6 ) 507 - 514 2022.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC
Calixarene derivatives are excellent host compounds for ionic species in liquid–liquid extraction. However, many studies using calixarene derivatives have been conducted using highly toxic chloroform as a solvent because of their poor solubility in typical hydrocarbons. In the present study, aromatic ethers were developed as solvents for calixarene derivatives to enhance their industrial applicability. The solubility of the calix[6]arene carboxylic acid derivative tOct[6]CH2COOH in 1-octoxybenzene (OB) and 1-butoxybenzene (BB) was 11.3 mM and 24.9 mM, respectively. The cationic guest molecule tryptophan methyl ester was extracted using the tOct[6]CH2COOH host in OB and BB. The cationic lysine-rich protein cytochrome c was also extracted using tOct[6]CH2COOH in BB as shown for tOct[6]CH2COOH in chloroform in previous studies. However, cytochrome c was not extracted using tOct[6]CH2COOH in OB and instead, precipitated. As tOct[6]CH2COOH stabilizes the ammonium group of biomolecules because of its suitable cavity size, the extraction of the tryptophan ester and cytochrome c using tOct[6]CH2COOH was much higher than those using the corresponding calix[4]arene and calix[8]arene derivatives. These results confirm that aromatic ethers are potential solvents for calixarene derivatives for the extraction of biomolecules.
DOI： 10.1007/s10847-022-01132-7
Other Link： https://link.springer.com/article/10.1007/s10847-022-01132-7/fulltext.html
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Inada A., Sawao A., Takahashi K., Oshima T.
Journal of Food Science 87 ( 3 ) 1174 - 1183 2022.3
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Food Science
Abstract: Although quercetin (Que) has many beneficial therapeutic effects on the human body, its oral bioavailability is poor because of its low water solubility. Herein, we describe the preparation of casein hydrolysate (Pepcas) and its use as a dispersant to enhance the water dispersibility of Que resulting in an improvement of its bioavailability. By complexation with Pepcas, the apparent solubility of Que in the complex (Que@Pepcas) was significantly increased under acidic and neutral conditions. Que@Pepcas was pre-digested in vitro using a simulated digestive juice, and a Caco-2 cell monolayer permeation assay was performed to evaluate the oral bioavailability of Que. The cumulative amount of Que that permeated the monolayer using Que@Pepcas after 8, 16, and 24 h was increased compared with a blank sample (Que@Blank), and the apparent permeation coefficient Papp of Que@Pepcas was approximately 2.6-fold better than that of Que@Blank. Practical Application: Pepcas can be used as a high absorption supplement and food additive, and our Pepcas complexation technique should be widely applicable to not only Que but also to other poorly water-soluble substances.
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Dominant factors that determine the dissolution state of complexes between poorly water-soluble ingredients and casein hydrolysate Reviewed International journal
Asuka Inada, Takumi Iwase, Tatsuya Oshima
Colloids and Surfaces B: Biointerfaces 208 112062 - 112062 2021.12
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
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Tatsuya Oshima, Koki Takahashi, Asuka Inada, Masao Yamasaki, Yumi Yamasaki, Nozomu Eto
Food Chemistry 360 129822 - 129822 2021.10
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
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Extraction of Au(III) using aromatic ethers via ion solvation from acidic chloride media: Structural factors that influence extraction Reviewed International journal
Tatsuya Oshima, Kiyoharu Matsuzaki, Asuka Inada, Kaoru Ohe
Separation and Purification Technology 258 118008 - 118008 2021.3
Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
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Effect of branch structure of thermoresponsive oligomers on draw solution performance in forward osmosis process Reviewed International journal
Asuka Inada, Kenichiro Yumiya, Kazuo Kumagai, Hideto Matsuyama
Colloids and Surfaces A: Physicochemical and Engineering Aspects 609 125659 - 125659 2021.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
A series of three types of oligomers—oligo(butylene oxide)n-block-oligo(ethylene oxide)m-block-oligo(butylene oxide)n oligomers (EBs), glycerol-oligo(ethylene oxide)m-block-(butylene oxide)n oligomers (GEBs), and pentaerythritol-oligo(ethylene oxide)m-block-(butylene oxide)n oligomers (PEBs)—having different branch structures were synthesized. EBs, GEBs, and PEBs had linear, three-branch, and four-branch structures, respectively. These oligomers were tested as draw solutes (DSs) for the forward osmosis (FO) process in order to reveal the effect of their branch structures on the FO performance and DS leakage from the FO membrane. The aqueous solutions of EBs, GEBs, and PEBs exhibited a typical lower critical solution temperature-type phase separation. The FO water fluxes in the case of EB, GEB, and PEB were 4.1–4.8 L m−2 h−1 (LMH) at an osmotic pressure of 28 bar, while the reverse solute fluxes (Js) were 0.79–1.83 gMH at DS concentrations corresponding to an osmotic pressure of 28 bar. Js decreased with an increase in the number of branches in the DS molecule, which improved the FO performance index. The results indicate the importance of introducing a branch structure into DS molecules to design useful DSs.
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Effect of the molecular weights of thermoresponsive polyalkylene glycol draw solutes on forward osmosis performance Reviewed International journal
Asuka Inada, Kazuo Kumagai, Hideto Matsuyama
Separation and Purification Technology 252 117462 - 117462 2020.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
In recent years, the forward osmosis (FO) process has been used as an alternative water purification technique. To achieve the FO process, one of the most important factors is the development of a draw solution (DS) that exhibits a high osmotic pressure and low solute leakage. In this study, poly(propylene glycol-ran-ethylene glycol) monobutyl ethers (PAGBs) with Mw = 278–3911 g/mol were studied and compared as thermoresponsive draw solutes for FO. All PAGBs exhibited phase separations with a lower critical solution temperature (LCST) between 42 and 53 °C. The osmotic pressure curve profiles differed among the tested PAGBs. Both the FO water flux Jw and reverse DS flux Js decreased with increasing molecular weights of PAGBs. The FO performance was measured by calculating Js/Jw. The value of Js decreased more drastically with increasing molecular weights of PAGBs than Jw. PAGBs with Mw range of 1810–3911 g/mol had the lowest Js/Jw ratio and were suitable as draw solutes for FO. These experimental results were confirmed by numerical calculations. Thermoresponsive DSs such as PAGBs may simplify the regeneration of DSs in FO systems.
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Development of amphiphilic metal-binding short peptides that change the dispersibility of paclitaxel upon complexation with intermediate metal(II) ions Reviewed International journal
Yuki Sakurai, Asuka Inada, Makoto Hitotsumatsu, Tatsuya Oshima
Journal of Drug Delivery Science and Technology 59 101882 - 101882 2020.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV