Pub Date : 2025-04-10eCollection Date: 2025-01-01DOI: 10.1080/14686996.2025.2474788
Shinsuke Ishihara, Jan Labuta, Jonathan P Hill, Takashi Nakanishi, Manabu Kakinohana, Nobuo Iyi
Inhaled nitric oxide (iNO) is a powerful therapy for the treatment of various cardiopulmonary and respiratory diseases. However, access to iNO therapy is often limited by the necessity of cumbersome gas tanks and/or elaborate gas blending apparatus. Here, we report a lightweight, inexpensive, and maintenance-free tablet that autonomously generates a therapeutic quantity of NO in air. The tablet is composed of a thimble filter paper containing a powdery mixture of nitrite (NO2‒)-type layered double hydroxide (NLDH) and ascorbic acid loaded on silica gel (AASiO2). NLDH by itself generates trace amounts of NO in the air due to the left-shifting of the protonation equilibrium of NO2‒ by aerial CO2 and H2O (2[NO2‒]LDH + CO2 + H2O 2HNO2↑ + [CO32‒]LDH), which is followed by disproportionation of 2HNO2 to NO, NO2 and H2O. In contrast, it was found that the protonation equilibrium can be shifted to the right side when volatile acid products (HNO2 and NO2) are readily converted to neutral NO over the AASiO2 reductant. Based on this, even a single tablet (containing 0.30 g NLDH and 0.90 g AASiO2) generates 5 ~ 20 ppm NO at 0.5 L/min for 24 h, which is sufficient to be useful for the relief of severe hypoxia caused by persistent pulmonary hypertension of the newborn (PPHN). Moreover, the tablet can be activated by exhaled breath for high-dose iNO therapy (80 ~ 180 ppm for several hours), revealing its potential utility for treating viral pneumonia. The NO tablet can be stored stably over long periods at ambient temperature in a gas barrier bag and has the potential to break the logistical, financial, and operational barriers that have long existed for the widespread implementation of iNO therapy.
吸入一氧化氮(iNO)是治疗各种心肺和呼吸系统疾病的有力疗法。然而,由于需要笨重的气罐和/或复杂的气体混合设备,使用iNO疗法往往受到限制。在这里,我们报告了一种重量轻,价格便宜,免维护的片剂,它可以自主地在空气中产生治疗量的NO。该片剂由含有载于硅胶(AASiO2)上的亚硝酸盐(NO2 -)型层状双氢氧化物(NLDH)和抗坏血酸的粉状混合物的顶针滤纸组成。空气中的CO2和H2O使NO2 -质子化平衡(2[NO2 -]LDH + CO2 + H2O + 2HNO2↑+ [co32 -]LDH)发生左移,NLDH自身在空气中产生微量NO,随后2HNO2歧化为NO、NO2和H2O。相反,当挥发性酸产物(HNO2和NO2)在AASiO2还原剂上容易转化为中性NO时,质子化平衡可以向右侧移动。基于此,即使是一片(含0.30 g NLDH和0.90 g AASiO2),以0.5 L/min的速度持续24 h,也能产生5 ~ 20 ppm的NO,足以用于缓解新生儿持续性肺动脉高压(PPHN)所致的严重缺氧。此外,该片剂可以通过呼出激活高剂量的碘治疗(80 ~ 180ppm,持续数小时),显示其治疗病毒性肺炎的潜在效用。NO片剂可以在室温下长期稳定地储存在气体屏障袋中,并且有可能打破长期存在的广泛实施iNO治疗的后勤,财务和操作障碍。
{"title":"NO tablet: autonomous generation of therapeutic nitric oxide in air through redox-promoted CO<sub>2</sub> adsorption.","authors":"Shinsuke Ishihara, Jan Labuta, Jonathan P Hill, Takashi Nakanishi, Manabu Kakinohana, Nobuo Iyi","doi":"10.1080/14686996.2025.2474788","DOIUrl":"https://doi.org/10.1080/14686996.2025.2474788","url":null,"abstract":"<p><p>Inhaled nitric oxide (iNO) is a powerful therapy for the treatment of various cardiopulmonary and respiratory diseases. However, access to iNO therapy is often limited by the necessity of cumbersome gas tanks and/or elaborate gas blending apparatus. Here, we report a lightweight, inexpensive, and maintenance-free tablet that autonomously generates a therapeutic quantity of NO in air. The tablet is composed of a thimble filter paper containing a powdery mixture of nitrite (NO<sub>2</sub> <sup>‒</sup>)-type layered double hydroxide (NLDH) and ascorbic acid loaded on silica gel (AASiO<sub>2</sub>). NLDH by itself generates trace amounts of NO in the air due to the left-shifting of the protonation equilibrium of NO<sub>2</sub> <sup>‒</sup> by aerial CO<sub>2</sub> and H<sub>2</sub>O (2[NO<sub>2</sub> <sup>‒</sup>]<sub>LDH</sub> + CO<sub>2</sub> + H<sub>2</sub>O <math><mo>⇌</mo></math> 2HNO<sub>2</sub>↑ + [CO<sub>3</sub> <sup>2‒</sup>]<sub>LDH</sub>), which is followed by disproportionation of 2HNO<sub>2</sub> to NO, NO<sub>2</sub> and H<sub>2</sub>O. In contrast, it was found that the protonation equilibrium can be shifted to the right side when volatile acid products (HNO<sub>2</sub> and NO<sub>2</sub>) are readily converted to neutral NO over the AASiO<sub>2</sub> reductant. Based on this, even a single tablet (containing 0.30 g NLDH and 0.90 g AASiO<sub>2</sub>) generates 5 ~ 20 ppm NO at 0.5 L/min for 24 h, which is sufficient to be useful for the relief of severe hypoxia caused by persistent pulmonary hypertension of the newborn (PPHN). Moreover, the tablet can be activated by exhaled breath for high-dose iNO therapy (80 ~ 180 ppm for several hours), revealing its potential utility for treating viral pneumonia. The NO tablet can be stored stably over long periods at ambient temperature in a gas barrier bag and has the potential to break the logistical, financial, and operational barriers that have long existed for the widespread implementation of iNO therapy.</p>","PeriodicalId":21588,"journal":{"name":"Science and Technology of Advanced Materials","volume":"26 1","pages":"2474788"},"PeriodicalIF":7.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-03eCollection Date: 2025-01-01DOI: 10.1080/14686996.2025.2485869
Yuichi Oshima, Takashi Shinohe
We demonstrated the epitaxial lateral overgrowth of m-plane α-Ga2O3 using halide vapor phase epitaxy. An m-plane α-Ga2O3/sapphire template with a patterned SiO2 mask was used as the substrate. The highest lateral growth rate for a radial spoke-wheel patterned mask was obtained when the spoke was perpendicular to the direction. In this case, the lateral-to-vertical growth rate ratio (L/V ratio), with L defined as the rate of increase in the width of an elongated α-Ga2O3 island, was as large as 5.8. This ratio was greater than that reported for an m-direction stripe mask on a-plane α-Ga2O3 by a factor of 3.3 and that for an a-direction stripe mask on c- and m-plane α-Ga2O3 by a factor of 13. The epitaxial lateral overgrowth (ELO) of α-Ga2O3 on a stripe mask (window/mask widths of 2.5 μm/7.5 μm) perpendicular to resulted in the selective nucleation of elongated α-Ga2O3 islands with a flat triangular cross-section on the window areas and their coalescence into a compact film. Transmission electron microscopy revealed that the dislocation density in the laterally grown area decreased drastically because the propagation of dislocations in the seed layer was effectively blocked by the mask. We believe these results greatly contribute to the realization of m-plane α-Ga2O3-based future power devices.
{"title":"Epitaxial lateral overgrowth of <i>m</i>-plane α-Ga<sub>2</sub>O<sub>3</sub> by halide vapor phase epitaxy.","authors":"Yuichi Oshima, Takashi Shinohe","doi":"10.1080/14686996.2025.2485869","DOIUrl":"https://doi.org/10.1080/14686996.2025.2485869","url":null,"abstract":"<p><p>We demonstrated the epitaxial lateral overgrowth of <i>m</i>-plane α-Ga<sub>2</sub>O<sub>3</sub> using halide vapor phase epitaxy. An <i>m</i>-plane α-Ga<sub>2</sub>O<sub>3</sub>/sapphire template with a patterned SiO<sub>2</sub> mask was used as the substrate. The highest lateral growth rate for a radial spoke-wheel patterned mask was obtained when the spoke was perpendicular to the <math> <mfenced><mrow><mn>11</mn> <mover><mn>2</mn> <mo>-</mo></mover> <mn>3</mn></mrow> </mfenced> </math> direction. In this case, the lateral-to-vertical growth rate ratio (<i>L</i>/<i>V</i> ratio), with <i>L</i> defined as the rate of increase in the width of an elongated α-Ga<sub>2</sub>O<sub>3</sub> island, was as large as 5.8. This ratio was greater than that reported for an <i>m</i>-direction stripe mask on <i>a</i>-plane α-Ga<sub>2</sub>O<sub>3</sub> by a factor of 3.3 and that for an <i>a</i>-direction stripe mask on <i>c</i>- and <i>m</i>-plane α-Ga<sub>2</sub>O<sub>3</sub> by a factor of 13. The epitaxial lateral overgrowth (ELO) of α-Ga<sub>2</sub>O<sub>3</sub> on a stripe mask (window/mask widths of 2.5 μm/7.5 μm) perpendicular to <math> <mfenced><mrow><mn>11</mn> <mover><mn>2</mn> <mo>-</mo></mover> <mn>3</mn></mrow> </mfenced> </math> resulted in the selective nucleation of elongated α-Ga<sub>2</sub>O<sub>3</sub> islands with a flat triangular cross-section on the window areas and their coalescence into a compact film. Transmission electron microscopy revealed that the dislocation density in the laterally grown area decreased drastically because the propagation of dislocations in the seed layer was effectively blocked by the mask. We believe these results greatly contribute to the realization of <i>m</i>-plane α-Ga<sub>2</sub>O<sub>3</sub>-based future power devices.</p>","PeriodicalId":21588,"journal":{"name":"Science and Technology of Advanced Materials","volume":"26 1","pages":"2485869"},"PeriodicalIF":7.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-03eCollection Date: 2025-01-01DOI: 10.1080/14686996.2025.2485668
Casey Y Huang, Helen Nguyen, David J Lundy, James J Lai
Extracellular vesicles (EVs) hold significant promise as biomarkers and therapeutics, yet their isolation remains challenging due to their low abundance and complex sample matrices. Here, we introduce EV-Osmoprocessor (EVOs), a novel device that leverages osmosis-driven filtration for rapid and efficient EV isolation. EVOs employs a high osmolarity polymer solution to concentrate EVs while simultaneously removing smaller contaminants. Compared to traditional methods such as ultracentrifugation and precipitation, EVOs offers speed and convenience, achieving a 50-fold volume reduction in under 2 h. Our results show that EVOs retained EVs and removed >99% albumin from the cell conditioned culture medium (CCM). The isolated EVs exhibited a particle size distribution centered around 140 nm, which was very similar to EVs isolated via precipitation or ultracentrifugation. The standalone EVOs process achieved a particle:protein ratio (EV purity) of ~107 particles/µg protein. Comprehensive characterization, including cryo-electron microscopy, validation of protein markers and known miRNA cargo confirmed the successful isolation of EVs. Functional assays, based on protection of cardiomyocytes from hypoxia/reoxygenation injury, demonstrated the bioactivity of EVOs-isolated EVs. Furthermore, we show that EVOs can be used to concentrate 30 ml of CCM into a 0.5 ml solution, which was then further processed with size-exclusion chromatography (SEC), improving EV purity to ~109 particles/µg protein. This work establishes EVOs as a promising tool for EV research and clinical applications, offering a streamlined approach to EV isolation with enhanced analytical performance.
{"title":"Rapid isolation of extracellular vesicles from stem cell conditioned medium using osmosis-driven filtration.","authors":"Casey Y Huang, Helen Nguyen, David J Lundy, James J Lai","doi":"10.1080/14686996.2025.2485668","DOIUrl":"https://doi.org/10.1080/14686996.2025.2485668","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) hold significant promise as biomarkers and therapeutics, yet their isolation remains challenging due to their low abundance and complex sample matrices. Here, we introduce EV-Osmoprocessor (EVOs), a novel device that leverages osmosis-driven filtration for rapid and efficient EV isolation. EVOs employs a high osmolarity polymer solution to concentrate EVs while simultaneously removing smaller contaminants. Compared to traditional methods such as ultracentrifugation and precipitation, EVOs offers speed and convenience, achieving a 50-fold volume reduction in under 2 h. Our results show that EVOs retained EVs and removed >99% albumin from the cell conditioned culture medium (CCM). The isolated EVs exhibited a particle size distribution centered around 140 nm, which was very similar to EVs isolated via precipitation or ultracentrifugation. The standalone EVOs process achieved a particle:protein ratio (EV purity) of ~10<sup>7</sup> particles/µg protein. Comprehensive characterization, including cryo-electron microscopy, validation of protein markers and known miRNA cargo confirmed the successful isolation of EVs. Functional assays, based on protection of cardiomyocytes from hypoxia/reoxygenation injury, demonstrated the bioactivity of EVOs-isolated EVs. Furthermore, we show that EVOs can be used to concentrate 30 ml of CCM into a 0.5 ml solution, which was then further processed with size-exclusion chromatography (SEC), improving EV purity to ~10<sup>9</sup> particles/µg protein. This work establishes EVOs as a promising tool for EV research and clinical applications, offering a streamlined approach to EV isolation with enhanced analytical performance.</p>","PeriodicalId":21588,"journal":{"name":"Science and Technology of Advanced Materials","volume":"26 1","pages":"2485668"},"PeriodicalIF":7.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Intense terahertz (THz) radiation in free space offers multifaceted capabilities for accelerating electron, understanding the mesoscale architecture in (bio)materials, elementary excitation and so on. Recently popularized spintronic THz emitters (STEs) with their versatility such as ultra-broadband, large-size and ease-for-integration have become one of the most promising alternative for the next generation of intense THz sources. Nevertheless, the typical W | Co Fe B | Pt necessitates an external-magnetic-field to saturate magnetization for stable operation, limiting its scalability for achieving higher THz field with uniform distribution over larger sample areas. Here we demonstrate the methodologies of enhancing the high-field THz radiation of external-magnetic-field-free IrMn | Co Fe B | W trilayer heterostructure via optimizing the substrate with superior thermal conductivity and integrating a one-dimensional photonic crystal (PC) structure to maximize the radiation efficiency. Under the excitation of a 1 kHz Ti: sapphire femtosecond laser amplifier with central wavelength of 800 nm, pulse duration of 35 fs, and maximum single pulse energy of 5.5 mJ, we successfully generate intense THz radiation with focal peak electric field up to 650 kV/cm with frequency range covering 0.1-5.5 THz from MgO-coated sample without external-magnetic-fields. These high-field STEs will also enable other applications such as ultra-broadband high-field THz spectroscopy and polarization-based large-size strong-field THz imaging.
自由空间中的强太赫兹(THz)辐射为加速电子、理解(生物)材料中的中尺度结构、初等激发等提供了多方面的能力。近年来普及的自旋电子太赫兹发射器(STEs)以其超宽带、大尺寸和易于集成等多功能性成为下一代强太赫兹源最有希望的替代方案之一。然而,典型的w| Co 20 Fe 60 b20 | Pt需要外部磁场来饱和磁化才能稳定运行,这限制了其可扩展性,无法在更大的样品面积上实现均匀分布的高太赫兹场。本文展示了通过优化具有优越导热性的衬底和集成一维光子晶体(PC)结构来增强无外磁场IrMn 3 | Co 20 Fe 60 b20 | W三层异质结构的高场太赫兹辐射的方法,以最大限度地提高辐射效率。在中心波长为800 nm、脉冲持续时间为35 fs、最大单脉冲能量为5.5 mJ的1 kHz钛蓝宝石飞秒激光放大器的激励下,我们成功地在没有外加磁场的情况下,从mgo涂层样品中产生了焦峰值电场高达650 kV/cm、频率范围为0.1 ~ 5.5 THz的强太赫兹辐射。这些高场STEs还将支持其他应用,如超宽带高场太赫兹光谱和基于偏振的大尺寸强场太赫兹成像。
{"title":"One-dimensional photonic crystal structure enhanced external-magnetic-field-free spintronic terahertz high-field emitter.","authors":"Zehao Yang, Jiahui Li, Shaojie Liu, Zejun Ren, Mingxuan Zhang, Chunyan Geng, Xiufeng Han, Caihua Wan, Xiaojun Wu","doi":"10.1080/14686996.2025.2478816","DOIUrl":"10.1080/14686996.2025.2478816","url":null,"abstract":"<p><p>Intense terahertz (THz) radiation in free space offers multifaceted capabilities for accelerating electron, understanding the mesoscale architecture in (bio)materials, elementary excitation and so on. Recently popularized spintronic THz emitters (STEs) with their versatility such as ultra-broadband, large-size and ease-for-integration have become one of the most promising alternative for the next generation of intense THz sources. Nevertheless, the typical W | Co <math><msub><mi> </mi> <mrow><mn>20</mn></mrow> </msub> </math> Fe <math><msub><mi> </mi> <mrow><mn>60</mn></mrow> </msub> </math> B <math><msub><mi> </mi> <mrow><mn>20</mn></mrow> </msub> </math> | Pt necessitates an external-magnetic-field to saturate magnetization for stable operation, limiting its scalability for achieving higher THz field with uniform distribution over larger sample areas. Here we demonstrate the methodologies of enhancing the high-field THz radiation of external-magnetic-field-free IrMn <math><msub><mi> </mi> <mn>3</mn></msub> </math> | Co <math><msub><mi> </mi> <mrow><mn>20</mn></mrow> </msub> </math> Fe <math><msub><mi> </mi> <mrow><mn>60</mn></mrow> </msub> </math> B <math><msub><mi> </mi> <mrow><mn>20</mn></mrow> </msub> </math> | W trilayer heterostructure via optimizing the substrate with superior thermal conductivity and integrating a one-dimensional photonic crystal (PC) structure to maximize the radiation efficiency. Under the excitation of a 1 kHz Ti: sapphire femtosecond laser amplifier with central wavelength of 800 nm, pulse duration of 35 fs, and maximum single pulse energy of 5.5 mJ, we successfully generate intense THz radiation with focal peak electric field up to 650 kV/cm with frequency range covering 0.1-5.5 THz from MgO-coated sample without external-magnetic-fields. These high-field STEs will also enable other applications such as ultra-broadband high-field THz spectroscopy and polarization-based large-size strong-field THz imaging.</p>","PeriodicalId":21588,"journal":{"name":"Science and Technology of Advanced Materials","volume":"26 1","pages":"2478816"},"PeriodicalIF":7.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study presents an approach for fabricating durable superhydrophobic surfaces on 3D-printed structures inspired by the architectural design of beehives. Using fused deposition modeling (FDM) 3D printing technology, hexagonal macrostructures were fabricated using polylactic acid (PLA) filament. These structures were designed to protect an inner layer of hydrophobic nanoparticles, which were deposited by a squeegee coating method and immobilized by a photocurable resin. The relationship between hexagonal area size (ranging from 24 to 200 mm2) and the durability of superhydrophobic properties under frictional stress was systematically investigated. Wettability and surface morphology analyses performed before and after the friction tests showed that structures with hexagonal areas between 40 and 80 mm2 retained superhydrophobicity even after 100 friction cycles, while larger hexagonal configurations exhibited diminished performance. To elucidate the underlying mechanisms, a theoretical model based on the Cassie-Baxter equation was developed and compared with experimental values alongside surface observations. This research advances the development of durable and functional superhydrophobic surfaces in 3D-printed materials, with promising implications for industries requiring water-repellent and self-cleaning technologies.
{"title":"Durable superhydrophobic surfaces on 3D-Printed structures inspired by beehive architecture.","authors":"Kengo Manabe, Makoto Saikawa, Tetsuhiro Iwai, Yasuo Norikane","doi":"10.1080/14686996.2025.2481824","DOIUrl":"https://doi.org/10.1080/14686996.2025.2481824","url":null,"abstract":"<p><p>This study presents an approach for fabricating durable superhydrophobic surfaces on 3D-printed structures inspired by the architectural design of beehives. Using fused deposition modeling (FDM) 3D printing technology, hexagonal macrostructures were fabricated using polylactic acid (PLA) filament. These structures were designed to protect an inner layer of hydrophobic nanoparticles, which were deposited by a squeegee coating method and immobilized by a photocurable resin. The relationship between hexagonal area size (ranging from 24 to 200 mm<sup>2</sup>) and the durability of superhydrophobic properties under frictional stress was systematically investigated. Wettability and surface morphology analyses performed before and after the friction tests showed that structures with hexagonal areas between 40 and 80 mm<sup>2</sup> retained superhydrophobicity even after 100 friction cycles, while larger hexagonal configurations exhibited diminished performance. To elucidate the underlying mechanisms, a theoretical model based on the Cassie-Baxter equation was developed and compared with experimental values alongside surface observations. This research advances the development of durable and functional superhydrophobic surfaces in 3D-printed materials, with promising implications for industries requiring water-repellent and self-cleaning technologies.</p>","PeriodicalId":21588,"journal":{"name":"Science and Technology of Advanced Materials","volume":"26 1","pages":"2481824"},"PeriodicalIF":7.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-24eCollection Date: 2025-01-01DOI: 10.1080/14686996.2025.2482514
Natsumi Ito, Ahmed Nabil, Koichiro Uto, Mitsuhiro Ebara
Ferroptosis, a form of non-apoptotic cell death, is emerging as a promising strategy for cancer therapy. Artesunate (ART), an extract obtained from the traditional Chinese medicine Qinghaosu, has been shown to exhibit anti-cancer activity by inducing ferroptosis in cancer cells. While previous research has focused on incorporating ART monomer into drug delivery systems for enhanced cancer targeting, this study presents 2-methacryloyloxyethyl ART polymer (poly(ARTEMA)), a novel polymer synthesized from ART for the first time. Our goal was evaluation of poly(ARTEMA) anticancer potential on breast cancer cells. First, we synthesized ARTEMA using esterification followed by its polymerization using the reversible addition-fragmentation chain transfer (RAFT) polymerization method. We evaluated its mechanism of action, focusing on two key pathways: temperature-triggered singlet oxygen generation and ferrous ions (Fe2+) release, both of which contribute to ferroptosis. Our results demonstrate that poly(ARTEMA) selectively generates singlet oxygen and Fe2+ due to the endoperoxide crosslinks, leading to cell death in breast cancer cells. We also investigated the anti-cancer potential of poly(ARTEMA) on breast cancer cells with and without a ferroptosis inhibitor. The IC50 values were 125 µM for the MCF-7 cancer cell line and 300 µM for the normal MCF-10 cell line, indicating enhanced toxicity toward cancer cell lines. These findings suggested that poly(ARTEMA) induces ferroptosis in cancer cells and may serve as a promising candidate for cancer therapy with minimal cytotoxicity. To the best of our knowledge, this report may be the first that successfully synthesized poly(ARTEMA) using ART, with its anticancer potential evaluation.
{"title":"Poly(ARTEMA), a novel artesunate-based polymer induces ferroptosis in breast cancer cells.","authors":"Natsumi Ito, Ahmed Nabil, Koichiro Uto, Mitsuhiro Ebara","doi":"10.1080/14686996.2025.2482514","DOIUrl":"https://doi.org/10.1080/14686996.2025.2482514","url":null,"abstract":"<p><p>Ferroptosis, a form of non-apoptotic cell death, is emerging as a promising strategy for cancer therapy. Artesunate (ART), an extract obtained from the traditional Chinese medicine Qinghaosu, has been shown to exhibit anti-cancer activity by inducing ferroptosis in cancer cells. While previous research has focused on incorporating ART monomer into drug delivery systems for enhanced cancer targeting, this study presents 2-methacryloyloxyethyl ART polymer (poly(ARTEMA)), a novel polymer synthesized from ART for the first time. Our goal was evaluation of poly(ARTEMA) anticancer potential on breast cancer cells. First, we synthesized ARTEMA using esterification followed by its polymerization using the reversible addition-fragmentation chain transfer (RAFT) polymerization method. We evaluated its mechanism of action, focusing on two key pathways: temperature-triggered singlet oxygen generation and ferrous ions (Fe<sup>2+</sup>) release, both of which contribute to ferroptosis. Our results demonstrate that poly(ARTEMA) selectively generates singlet oxygen and Fe<sup>2+</sup> due to the endoperoxide crosslinks, leading to cell death in breast cancer cells. We also investigated the anti-cancer potential of poly(ARTEMA) on breast cancer cells with and without a ferroptosis inhibitor. The IC<sub>50</sub> values were 125 µM for the MCF-7 cancer cell line and 300 µM for the normal MCF-10 cell line, indicating enhanced toxicity toward cancer cell lines. These findings suggested that poly(ARTEMA) induces ferroptosis in cancer cells and may serve as a promising candidate for cancer therapy with minimal cytotoxicity. To the best of our knowledge, this report may be the first that successfully synthesized poly(ARTEMA) using ART, with its anticancer potential evaluation.</p>","PeriodicalId":21588,"journal":{"name":"Science and Technology of Advanced Materials","volume":"26 1","pages":"2482514"},"PeriodicalIF":7.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
4-Phenylbutyric acid (PBA) is a small molecule with promising therapeutic potential for treating various diseases, including cancer and neurodegenerative disorders, due to its dual ability to reduce endoplasmic reticulum stress and inhibit histone deacetylases. However, its clinical application is hindered by rapid clearance from the body, necessitating frequent dosing that increases the risk of adverse effects. To address these limitations, we developed a nanoparticle-based prodrug (NanoPBA) utilizing the amphiphilic block copolymer poly(ethylene glycol)-b-poly(vinyl 4-phenylbutyrate) [PEG-b-P(VPBA)]. This system self-assembles into micelles, enabling controlled and sustained PBA delivery. The synthesis and characterization of NanoPBA revealed its high stability under physiological conditions and enzyme-responsive PBA release. NanoPBA demonstrated a controlled release profile invitro, reducing burst release while maintaining therapeutic efficacy. Cytotoxicity assays using normal cell lines, including endothelial cells (BAEC), macrophages (RAW264.7), and rat gastric cells (RGM-1), showed minimal cytotoxic effects compared to the parent low-molecular-weight PBA. Furthermore, invivo studies conducted in healthy C57BL/6J mice confirmed NanoPBA's biocompatibility, with no significant adverse effects observed at therapeutic doses ranging from 200 to 500 mg-PBA/kg via oral administration. In conclusion, NanoPBA offers a controlled release profile, enhanced biocompatibility, and reduced toxicity, addressing the limitations associated with conventional PBA administration. These attributes make NanoPBA a promising candidate for improving the therapeutic efficacy and safety of PBA in clinical applications, particularly in diseases where maintaining consistent drug levels is crucial for treatment outcomes.
{"title":"Development and evaluation of a self-assembled nanoparticle-based prodrug for sustained delivery of 4-phenylbutyric acid.","authors":"Kikka Maeda, Babita Shashni, Hirofumi Matsui, Yukio Nagasaki","doi":"10.1080/14686996.2025.2482512","DOIUrl":"https://doi.org/10.1080/14686996.2025.2482512","url":null,"abstract":"<p><p>4-Phenylbutyric acid (PBA) is a small molecule with promising therapeutic potential for treating various diseases, including cancer and neurodegenerative disorders, due to its dual ability to reduce endoplasmic reticulum stress and inhibit histone deacetylases. However, its clinical application is hindered by rapid clearance from the body, necessitating frequent dosing that increases the risk of adverse effects. To address these limitations, we developed a nanoparticle-based prodrug (Nano<sup>PBA</sup>) utilizing the amphiphilic block copolymer poly(ethylene glycol)-<i>b</i>-poly(vinyl 4-phenylbutyrate) [PEG-<i>b</i>-P(VPBA)]. This system self-assembles into micelles, enabling controlled and sustained PBA delivery. The synthesis and characterization of Nano<sup>PBA</sup> revealed its high stability under physiological conditions and enzyme-responsive PBA release. Nano<sup>PBA</sup> demonstrated a controlled release profile <i>in</i> <i>vitro</i>, reducing burst release while maintaining therapeutic efficacy. Cytotoxicity assays using normal cell lines, including endothelial cells (BAEC), macrophages (RAW264.7), and rat gastric cells (RGM-1), showed minimal cytotoxic effects compared to the parent low-molecular-weight PBA. Furthermore, <i>in</i> <i>vivo</i> studies conducted in healthy C57BL/6J mice confirmed Nano<sup>PBA</sup>'s biocompatibility, with no significant adverse effects observed at therapeutic doses ranging from 200 to 500 mg-PBA/kg via oral administration. In conclusion, Nano<sup>PBA</sup> offers a controlled release profile, enhanced biocompatibility, and reduced toxicity, addressing the limitations associated with conventional PBA administration. These attributes make Nano<sup>PBA</sup> a promising candidate for improving the therapeutic efficacy and safety of PBA in clinical applications, particularly in diseases where maintaining consistent drug levels is crucial for treatment outcomes.</p>","PeriodicalId":21588,"journal":{"name":"Science and Technology of Advanced Materials","volume":"26 1","pages":"2482512"},"PeriodicalIF":7.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-07eCollection Date: 2025-01-01DOI: 10.1080/14686996.2025.2475738
Chengyang Liu, Masafumi Yoshio
This study introduces a novel supramolecular thermotropic columnar liquid-crystalline (LC) electrolyte tailored for high-performance ionic electroactive polymer (iEAP) actuators. The electrolyte is designed by integrating lithium salts into a taper-shaped molecule with bisphosphate moieties (BPO), which self-assembles into a columnar hexagonal (Colh) phase, forming 3D continuous ion-conductive pathways. This architecture achieves high ionic conductivity of up to 2 × 10-4 S cm-1 at room temperature. An actuator was fabricated by embedding this electrolyte into a microporous polyethylene membrane, sandwiched between PEDOT:PSS electrodes. The resulting device exhibits exceptional performance, achieving a bending strain of 0.52% and a force output of 0.5 mN under a ± 2 V, along with outstanding durability, retaining its performance over 9000 cycles. These results underscore the potential of 3D ion-conductive LC electrolytes in advancing iEAP actuator technologies, paving the way for innovative applications in tactile interfaces and soft robotics.
本研究介绍了一种用于高性能离子电活性聚合物(iEAP)致动器的新型超分子热致性柱状液晶(LC)电解质。电解质是通过将锂盐整合成具有二磷酸基团(BPO)的锥形分子来设计的,该分子可自组装成柱状六方(Colh)相,形成3D连续的离子导电途径。该结构在室温下可实现高达2 × 10-4 S cm-1的高离子电导率。通过将电解质嵌入到夹在PEDOT:PSS电极之间的微孔聚乙烯膜中,制造了致动器。由此产生的器件表现出卓越的性能,在±2 V下实现0.52%的弯曲应变和0.5 mN的力输出,以及出色的耐久性,在9000次循环中保持其性能。这些结果强调了3D离子导电LC电解质在推进iEAP执行器技术方面的潜力,为触觉界面和软机器人的创新应用铺平了道路。
{"title":"Electroactive soft actuators utilizing PEDOT:PSS and 3D lithium-ion-conducting phosphate columnar liquid crystals embedded in a porous polyethylene membrane.","authors":"Chengyang Liu, Masafumi Yoshio","doi":"10.1080/14686996.2025.2475738","DOIUrl":"10.1080/14686996.2025.2475738","url":null,"abstract":"<p><p>This study introduces a novel supramolecular thermotropic columnar liquid-crystalline (LC) electrolyte tailored for high-performance ionic electroactive polymer (iEAP) actuators. The electrolyte is designed by integrating lithium salts into a taper-shaped molecule with bisphosphate moieties (BPO), which self-assembles into a columnar hexagonal (Col<sub>h</sub>) phase, forming 3D continuous ion-conductive pathways. This architecture achieves high ionic conductivity of up to 2 × 10<sup>-4</sup> S cm<sup>-1</sup> at room temperature. An actuator was fabricated by embedding this electrolyte into a microporous polyethylene membrane, sandwiched between PEDOT:PSS electrodes. The resulting device exhibits exceptional performance, achieving a bending strain of 0.52% and a force output of 0.5 mN under a ± 2 V, along with outstanding durability, retaining its performance over 9000 cycles. These results underscore the potential of 3D ion-conductive LC electrolytes in advancing iEAP actuator technologies, paving the way for innovative applications in tactile interfaces and soft robotics.</p>","PeriodicalId":21588,"journal":{"name":"Science and Technology of Advanced Materials","volume":"26 1","pages":"2475738"},"PeriodicalIF":7.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-07eCollection Date: 2025-01-01DOI: 10.1080/14686996.2025.2475736
Jun Kobayashi, Masamichi Nakayama, Kenichi Nagase
Dynamically thermoresponsive biomaterials, particularly those utilizing poly(N-isopropylacrylamide) (PNIPAAm), have attracted much attention in biomedical applications due to their reversible phase transition near body temperature. These biomaterials provide innovations across drug delivery system, chromatography, and tissue engineering. Molecular designs, such as the incorporation of hydrophilic comonomers or graft copolymers in PNIPAAm hydrogels, enhance rapid kinetics of the gels when jumping the temperature across the phase transition temperature, because of avoiding 'skin layer' formation on the surface of the gels. Nanocarriers possessing PNIPAAm coronas facilitate spatial drug delivery and temporally on-demand drug release to targeted cancers in combination with hyperthermic therapy. Downsizing of PNIPAAm hydrogels accelerates the kinetics of shrinkage/swelling, leading to applications as thermoresponsive chromatographic matrices and cell cultureware. PNIPAAm-modified surfaces support thermoresponsive cell culture systems for the non-invasive recovery of intact cell sheets, enabling advanced regenerative therapies and layered 3D tissue formation. Recent developments also integrate growth factor delivery for sustained cell stimulation on culturewares. Newly developed biomaterials, including dynamically thermoresponsive PNIPAAm, are expected to expand the opportunity for novel treatment technologies such as targeted therapies and regenerative medicine.
{"title":"Molecular design of dynamically thermoresponsive biomaterials.","authors":"Jun Kobayashi, Masamichi Nakayama, Kenichi Nagase","doi":"10.1080/14686996.2025.2475736","DOIUrl":"10.1080/14686996.2025.2475736","url":null,"abstract":"<p><p>Dynamically thermoresponsive biomaterials, particularly those utilizing poly(<i>N</i>-isopropylacrylamide) (PNIPAAm), have attracted much attention in biomedical applications due to their reversible phase transition near body temperature. These biomaterials provide innovations across drug delivery system, chromatography, and tissue engineering. Molecular designs, such as the incorporation of hydrophilic comonomers or graft copolymers in PNIPAAm hydrogels, enhance rapid kinetics of the gels when jumping the temperature across the phase transition temperature, because of avoiding 'skin layer' formation on the surface of the gels. Nanocarriers possessing PNIPAAm coronas facilitate spatial drug delivery and temporally on-demand drug release to targeted cancers in combination with hyperthermic therapy. Downsizing of PNIPAAm hydrogels accelerates the kinetics of shrinkage/swelling, leading to applications as thermoresponsive chromatographic matrices and cell cultureware. PNIPAAm-modified surfaces support thermoresponsive cell culture systems for the non-invasive recovery of intact cell sheets, enabling advanced regenerative therapies and layered 3D tissue formation. Recent developments also integrate growth factor delivery for sustained cell stimulation on culturewares. Newly developed biomaterials, including dynamically thermoresponsive PNIPAAm, are expected to expand the opportunity for novel treatment technologies such as targeted therapies and regenerative medicine.</p>","PeriodicalId":21588,"journal":{"name":"Science and Technology of Advanced Materials","volume":"26 1","pages":"2475736"},"PeriodicalIF":7.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-06eCollection Date: 2025-01-01DOI: 10.1080/14686996.2025.2467617
Cindy L Atencio-Martinez, Alexandre Lancelot, Jonathan J Wilker
Catechol-containing polymers inspired by marine mussels have gained significant interest in recent years, leading to applications in several fields. Among these polymer systems, poly(vinylcatechol-styrene) (PVCS) has become a popular option due to its exceptional underwater adhesion strength, with readily available monomers and diverse synthetic routes being available. However, the translation of any novel adhesive chemistry from academic research to real-world applications can be challenging. Acrylates, epoxies, and urethanes were introduced to markets over half a century ago and remain dominant. However, bonding in wet environments remains lacking. The work presented here addresses this gap by focusing on the formulation of PVCS-based adhesives for conditions outside of the research lab. An emphasis was placed on handling properties when working underwater. A collection of different substrates were bonded together and several commercial glues provided benchmarks. Environmental conditions were studied to broaden the potential applications of PVCS adhesives in underwater settings. By optimizing formulations, we present an adhesive system that retains the superior underwater bonding of PVCS while also offering enhanced workability. This approach may help open the door to utilization of a new adhesive chemistry for underwater applications.
{"title":"Formulation of catechol-containing adhesives for enhanced underwater bonding and workability.","authors":"Cindy L Atencio-Martinez, Alexandre Lancelot, Jonathan J Wilker","doi":"10.1080/14686996.2025.2467617","DOIUrl":"10.1080/14686996.2025.2467617","url":null,"abstract":"<p><p>Catechol-containing polymers inspired by marine mussels have gained significant interest in recent years, leading to applications in several fields. Among these polymer systems, poly(vinylcatechol-styrene) (PVCS) has become a popular option due to its exceptional underwater adhesion strength, with readily available monomers and diverse synthetic routes being available. However, the translation of any novel adhesive chemistry from academic research to real-world applications can be challenging. Acrylates, epoxies, and urethanes were introduced to markets over half a century ago and remain dominant. However, bonding in wet environments remains lacking. The work presented here addresses this gap by focusing on the formulation of PVCS-based adhesives for conditions outside of the research lab. An emphasis was placed on handling properties when working underwater. A collection of different substrates were bonded together and several commercial glues provided benchmarks. Environmental conditions were studied to broaden the potential applications of PVCS adhesives in underwater settings. By optimizing formulations, we present an adhesive system that retains the superior underwater bonding of PVCS while also offering enhanced workability. This approach may help open the door to utilization of a new adhesive chemistry for underwater applications.</p>","PeriodicalId":21588,"journal":{"name":"Science and Technology of Advanced Materials","volume":"26 1","pages":"2467617"},"PeriodicalIF":7.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}