Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acsabm.5c00595

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.matlet.2025.138115

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Authorship：Lead author   Language：Japanese   Publishing type：Part of collection (book)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

There are two types of carbonated apatite (cap): A‐type and B‐type, where carbonate ions substitute for hydroxyl sites in A‐CAp and phosphate sites in B‐CAp. Despite the known capacity of CAp in supporting the activities of bone cells, the distinct potential of A‐CAp and B‐CAp as porous bone grafts is unclear. This study aimed to fabricate porous A‐CAp and B‐CAp and evaluate their biological activities in vitro and in vivo as compared to stoichiometric hydroxyapatite (HAp). Gelatin‐casting and freeze‐drying followed by sintering were used to produce A‐ and B‐CAp with high porosity ∼70%, pore sizes ∼100 µm, and high strength < 3 MPa. The carbonate contents of A‐ and B‐CAp were 3.83 and 4.5 wt%, respectively, as determined by thermal gravimetric analysis and calculations based on thermal decomposition reactions. A‐ and B‐CAp dissolved faster than HAp. A‐CAp had a higher affinity for albumin but poorer osteoblastic cell attachment, while both A‐ and B‐CAp had lower proliferation rates than HAp. After 2 weeks implantation in vivo, A‐CAp and HAp showed limited bone formation, whereas B‐CAp demonstrated bone ingrowth. Notably, A‐CAp showed enhanced osteoclast maturation. Both A‐CAp and B‐CAp were degradable after 8 weeks post‐implantation. Structural features and carbonate substitution types elicit different output on physicochemical, osteoconductivity, and degradability.

DOI： 10.1111/jace.20389

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acsbiomaterials.4c01617

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

Dually-labelled polymeric micelles allowed tracing both the probe location and the levels of singlet oxygen (¹O₂) in biological systems.

DOI： 10.1039/d4me00105b

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ceramint.2024.07.349

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

3D multicellular self-organized cluster models, e.g., organoids are promising tools for developing new therapeutic modalities including gene and cell therapies, pharmacological mechanistic and screening assays. Various applications of these models have been used extensively for decades, however, the mechanisms of cluster formation, maintenance, and degradation of these models are not even known over in-vitro-life-time. To explore such advantageous models mimicking native tissues or organs, it is necessary to understand aforementioned mechanisms. Herein, we intend to clarify the mechanisms of the formation of cell clusters. We previously demonstrated that primary chondrocytes isolated from distinct longitudinal depth zones in articular cartilage formed zone-specific spherical multicellular clusters in vitro. To elucidate the mechanisms of such cluster formation, we simulated it using the computational Cellular Potts Model with parameters were translated from gene expression levels and histological characteristics corresponding to interactions between cell and extracellular matrix. This simulation in silico was validated morphologically with cluster formation in vitro and vice versa. Since zone specific chondrocyte cluster models in silico showed similarity with corresponding in vitro model, the in silico has a potential to be used for prediction of the 3D multicellular in vitro models used for development, disease, and therapeutic models.

DOI： 10.3389/fbioe.2024.1440434

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Language：English   Publishing type：Research paper (scientific journal)  

Early and accurate cancer diagnosis is crucial for improving patient survival rates. Luminescent nanoparticles have emerged as a promising tool in fluorescence bioimaging for cancer diagnosis. To enhance diagnostic accuracy, ligands promoting endocytosis into cancer cells are commonly incorporated onto nanoparticle surfaces. Folic acid (FA) is one such ligand, known to specifically bind to folate receptors (FR) overexpressed in various cancer cells such as cervical and ovarian carcinoma. Therefore, surface modification of luminescent nanoparticles with FA can enhance both luminescence efficiency and diagnostic accuracy. In this study, luminescent europium-doped hydroxyapatite (EuHAp) nanocrystals were prepared via hydrothermal method and subsequently modified with (3-Aminopropyl)triethoxysilane (APTES) followed by FA to target FR-positive human cervical adenocarcinoma cell line (HeLa) cells. The sequential grafting of APTES and then FA formed a robust covalent linkage between the nanocrystals and FA. Rod-shaped FA-modified EuHAp nanocrystals, approximately 100 nm in size, exhibited emission peaks at 589, 615, and 650 nm upon excitation at 397 nm. Despite a reduction in photoluminescence intensity following FA modification, fluorescence microscopy revealed a remarkable 120-fold increase in intensity compared to unmodified EuHAp, attributed to the enhanced uptake of FA-modified EuHAp. Additionally, confocal microscope observations confirmed the specificity and the internalization of FA-modified EuHAp nanocrystals in HeLa cells. In conclusion, the modification of EuHAp nanocrystals with FA presents a promising strategy to enhance the diagnostic potential of cancer bioimaging probes.

DOI： 10.1016/j.colsurfb.2024.113975

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

Bismuth (Bi(III)) substitution in hydroxyapatite (HAp) lattice confers unique properties such as antibacterial, catalytic, radiosensitization, and conductive properties while preserving the innate bioactivity. Understanding the local structural changes upon Bi3+ substitution is essential for controlling the stability and optimizing the properties of HAp. Despite numerous experimental studies, the precise substitution behaviors, such as site preference and structural stability, remain incompletely understood. In this study, the substitution behavior of Bi(III) into the HAp lattice with formula of Ca9Bi(PO4)6(O)(OH) was investigated via first-principles simulation by implementing density functional theory. Energy calculations showed that Bi3+ preferentially occupies the Ca(2) site with an energy difference of ∼0.02 eV per atom. Local structure analysis revealed higher bond population values and an oxygen coordination shift from 7 to 6 for the Ca(2) site, attributed to the greater covalent interactions and its flexible environment accommodating the bulky Bi3+ ion and its stereochemically active lone pair. This work provides the first comprehensive investigation on Bi3+ ion substitution site preference in HAp using first-principles simulations.

DOI： 10.1039/d4cp00864b

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

<jats:p>mRNA-based nanocarriers are made of amine-derived cationic materials. Here, we showed the potential of cationic tirphenylphosphonium (TPP) for developing nanocarriers with improved mRNA delivery efficiency.</jats:p>

DOI： 10.1039/d4mh00325j

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Recently, bottom-up technologies, in particular the utilization of self-assembly of functional polymers to form nanostructures in solutions have been collecting attention. These technologies are being explored for various applications, especially for usage in therapeutics. One of the goals of such studies is to develop a drug delivery system (DDS) that delivers bioactive substances to specific targets within our body, eliciting the desired functionality. The authors have been developing "nanomachines" using biocompatible polymers to safely and efficiently deliver drugs mainly to tumors. The aim of this study is to utilize our expertise in designing a nanomachine to develop a cutting-edge nanomachine that can efficiently penetrate the blood-brain barrier (BBB) and deliver drugs to the brain parenchyma. Furthermore, leveraging this "nanomachine" technology, the authors are advancing the "Hayabusa Nanomachine," which can non-invasively collect and detect brain molecules, correlating them with various biological processes, ultimately leading to a better understanding of brain function and diseases. This paper also introduces the concept and ongoing efforts to the development of "Hayabusa Nanomachines," which have the potential to revolutionize existing approaches in this field.

DOI： 10.1254/fpj.23042

PubMed

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Medulloblastoma is a life-threatening disease with poor therapeutic outcomes. In chemotherapy, low drug accumulation has been a cause of these outcomes. Such inadequate response to treatments has been associated with low drug accumulation, particularly with a limited cellular uptake of drugs. Recently, the conjugation of drugs to ligand molecules with high affinity to tumor cells has attracted much attention for enhancing drug internalization into target cells. Moreover, combining tumor-targeting ligands with nano-scaled drug carriers can potentially improve drug loading capacity and the versatility of the delivery. Herein, we focused on the possibility of targeting CD276/B7-H3, which is highly expressed on the medulloblastoma cell membrane, as a strategy for enhancing the cellular uptake of ligand-installed nanocarriers. Thus, anti-CD276 antibodies were conjugated on the surface of model nanocarriers based on polyion complex micelles (PIC/m) via click chemistry. The results showed that the anti-CD276 antibody-installed PIC/m improved intracellular delivery into CD276-expressing medulloblastoma cells in a CD276-dependent manner. Moreover, increasing the number of antibodies on the surface of micelles improved the cellular uptake efficiency. These observations indicate the potential of anti-CD276 antibody-installed nanocarriers for promoting drug delivery in medulloblastoma.

DOI： 10.3390/polym15071808

PubMed

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：{MDPI} {AG}  

DOI： 10.3390/ijms23126686

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

DOI： 10.1016/j.jddst.2021.102375

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.30880/ijie.2021.13.05.011

Web of Science

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Language：English   Publishing type：Research paper (international conference proceedings)  

DOI： 10.1109/IECBES48179.2021.9398758

Web of Science

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.langmuir.0c00694

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：The Electrochemical Society  

A hydrogel is constructed of polymers that are crosslinked to form a three-dimensional network structure with water absorbed within. When using hydrogel as a biomaterial, wettability is one of the important physical properties as it largely affects how protein and cells can adhere on its surface. In previous studies aiming to evaluate the wettability of hydrogel, the affect was evaluated by changing the composition and side chain of the polymer chain constituting the network structure for existing hydrogels such as agarose and gelatin. However, the existing network structure of hydrogel has spatial heterogeneity and topological heterogeneity, and therefore it has been said to be difficult to independently determine which parameter of the network structure was truly affecting wettability. In this research, in order to solve this problem, we aimed to independently and quantitatively evaluate the effect of each parameter on wettability by using the Tetra-PEG gel.Tetra-PEG gel is a type of gel that is composed of two symmetrical tetra-branched structure of Tetra-amine-terminated PEG (Tetra-PEG-NH₂) and Tetra-OSu-terminated PEG (Tetra-PEG-OSu). Gelation is done simply by mixing equal amounts of these polymer solutions. As our first attempt, we controlled the polymer volume fraction of the hydrogel and the molecular weight between the crosslinking points by adjusting the concentration of the polymer solution and the molecular weight of the polymer, respectively. To evaluate the effect of charged groups, p-tuned Tetra-PEG gel having ion pairs of positive and negative charged groups was prepared. On the other hand, r-tuned Tetra - PEG gel was prepared to evaluate the effect of the presence of ionic pairs on wettability. Positive or negative charged groups were introduced into the system by changing the mixing ratio of Tetra-PEG-NH₂ and Tetra-PEG-Osu, and by so causing either polymer to excessively exist within the hydrogel.Wettability was evaluated through static contact angle measurement. 2 uL of water droplets were dropped onto the surface of the hydrogel, and the contact angle immediately after the dropping was measured. The contact angle measurement results for 5k, 10k, 20k, and 40k Tetra-PEG gel are shown in Fig. 1. For 5k Tetra - PEG gel, contact angle showed values less than 30 degrees, and contact angle showed a decrease with increase in volume fraction. However, contact angle for 5k polymer suddenlyd increase at volume fraction of 0.11.To give a logical and consistent explanation to this result, we introduced the idea of mobility of the polymer chains into the discussion of how the wettability of the hydrogel was determined. When the polymer molecular weight is large, the polymer chain is largely movable, so the PEG chain is bound in the bulk due to the intermolecular force with the water molecules in the gel . As a result, the surface exhibited a hydrophobic property. On the other hand, when the polymer molecular weight is small like 5k Tetra-PEG gel, it is considered that the surface was kept relatively hydrophilic because the polymer chain was bound near the surface and pulled the droplet inwards. Furthermore, in the region of low polymer molecular weight such as 5k Tetra-PEG gel, it is considered that if the volume fraction increases, the polymer chain becomes difficult to move and the hydrophilicity also increases.  Fig. 2 shows the results of contact angle measurement when the charged group concentration was changed. At polymer volume fractions 0.066, 0.081, and 0.096, the contact angle decreased with an increase in the charged group concentration, but decrease in contact angle could not be confirmed at polymer volume fraction of 0.50. In addition, it was confirmed from Fig. 3 that the contact angle of r-tuned Tetra-PEG gel was lower than that of p-tuned Tetra-PEG gel.These results are thought to be because the charged group acted as a hydrophilic group for water molecules which are polar molecules. Wettability did not decrease with p-tuned Tetra-PEG gel with a volume fraction of 0.050, because there were too few charged groups (5 mol/m³) per volume and was not sufficient to visibly affect the surface characteristics. In addition, since the p-tuned Tetra-PEG gel in which the ion pair exists exhibits lower wettability than the r-tuned Tetra-PEG gel, the affinity between the polymer and water decreases due to the presence of the ion pair. As a conclusion, it was revealed that polymer molecular weight greatly affects the mobility of the polymer chain and the wettability, and the wettability is increased by the introduction of the charged group, and when the ion pair is present, wettability decreases.





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DOI： 10.1149/ma2018-03/1/95

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Other Link： https://iopscience.iop.org/article/10.1149/MA2018-03/1/95/pdf