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Green Nanotechnology Through Papain Nanoparticles: Preclinical in vitro and in vivo Evaluation of Imaging Triple-Negative Breast Tumors. 通过木瓜蛋白酶纳米颗粒实现绿色纳米技术:三阴性乳腺肿瘤成像的临床前体内外评估
IF 4.9 Q2 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-09-25 eCollection Date: 2024-01-01 DOI: 10.2147/NSA.S474194
Aryel H Ferreira, Fábio L N Marques, Caroline C Real, Velaphi C Thipe, Lucas F Freitas, Caroline S A Lima, Larissa Estessi de Souza, Mara S Junqueira, Daniele de Paula Faria, Gustavo H C Varca, Ademar B Lugão, Kattesh V Katti

Background: Recent advancements in nanomedicine and nanotechnology have expanded the scope of multifunctional nanostructures, offering innovative solutions for targeted drug delivery and diagnostic agents in oncology and nuclear medicine. Nanoparticles, particularly those derived from natural sources, hold immense potential in overcoming biological barriers to enhance therapeutic efficacy and diagnostic accuracy. Papain, a natural plant protease derived from Carica papaya, emerges as a promising candidate for green nanotechnology-based applications due to its diverse medicinal properties, including anticancer properties.

Purpose: This study presents a novel approach in nanomedicine and oncology, exploring the potential of green nanotechnology by developing and evaluating technetium-99m radiolabeled papain nanoparticles (99mTc-P-NPs) for imaging breast tumors. The study aimed to investigate the efficacy and specificity of these nanoparticles in breast cancer models through preclinical in vitro and in vivo assessments.

Methods: Papain nanoparticles (P-NPs) were synthesized using a radiation-driven method and underwent thorough characterization, including size, surface morphology, surface charge, and cytotoxicity assessment. Subsequently, P-NPs were radiolabeled with technetium-99m (99mTc), and in vitro and in vivo studies were conducted to evaluate cellular uptake at tumor sites, along with biodistribution, SPECT/CT imaging, autoradiography, and immunohistochemistry assays, using breast cancer models.

Results: The synthesized P-NPs exhibited a size mean diameter of 9.3 ± 1.9 nm and a spherical shape. The in vitro cytotoxic activity of native papain and P-NPs showed low cytotoxicity in HUVEC, MDA-MB231, and 4T1 cells. The achieved radiochemical yield was 94.2 ± 3.1% that were sufficiently stable (≥90%) for 6 h. The tumor uptake achieved in the 4T1 model was 2.49 ± 0.32% IA/g at 2 h and 1.51 ± 0.20% IA/g at 6 h. In the spontaneous breast cancer model, 1.19 ± 0.20% IA/g at 2 h and 0.86 ± 0.31% IA/g at 6 h. SPECT/CT imaging has shown substantial tumor uptake of the new nanoradiopharmaceutical and clear tumor visualization. 99mTc-P-NPs exhibited a high affinity to tumoral cells confirmed by ex vivo autoradiography and immunohistochemistry assays.

Conclusion: The findings underscore the potential of green nanotechnology-driven papain nanoparticles as promising agents for molecular imaging of breast and other tumors through SPECT/CT imaging. The results represent a substantial step forward in the application of papain nanoparticles as carriers of diagnostic and therapeutic radionuclides to deliver diagnostic/therapeutic payloads site-specifically to tumor sites for the development of a new generation of nanoradiopharmaceuticals.

背景:纳米医学和纳米技术的最新进展扩大了多功能纳米结构的范围,为肿瘤学和核医学中的靶向给药和诊断制剂提供了创新解决方案。纳米粒子,尤其是那些从天然来源提取的纳米粒子,在克服生物障碍以提高疗效和诊断准确性方面具有巨大的潜力。木瓜蛋白酶是从木瓜中提取的一种天然植物蛋白酶,因其多种药用特性(包括抗癌特性)而成为绿色纳米技术应用的理想候选物质。目的:本研究提出了一种纳米医学和肿瘤学的新方法,通过开发和评估用于乳腺肿瘤成像的锝-99m放射性标记木瓜蛋白酶纳米颗粒(99mTc-P-NPs),探索绿色纳米技术的潜力。该研究旨在通过临床前体外和体内评估,研究这些纳米颗粒在乳腺癌模型中的疗效和特异性:方法:采用辐射驱动法合成木瓜蛋白酶纳米颗粒(P-NPs),并对其进行全面表征,包括尺寸、表面形态、表面电荷和细胞毒性评估。随后,用锝-99m (99mTc)对 P-NPs 进行了放射性标记,并利用乳腺癌模型进行了体外和体内研究,以评估肿瘤部位的细胞摄取情况,同时还进行了生物分布、SPECT/CT 成像、自显影和免疫组化检测:合成的 P-NPs 的平均直径为 9.3 ± 1.9 nm,呈球形。原生木瓜蛋白酶和 P-NPs 对 HUVEC、MDA-MB231 和 4T1 细胞的体外细胞毒性较低。在4T1模型中,2小时的肿瘤摄取率为2.49±0.32% IA/g,6小时为1.51±0.20% IA/g。在自发性乳腺癌模型中,2 小时的摄取量为 1.19 ± 0.20% IA/g,6 小时的摄取量为 0.86 ± 0.31% IA/g。SPECT/CT 成像显示,新型纳米放射药物被肿瘤大量摄取,肿瘤显像清晰。99m锝-P-NPs对肿瘤细胞具有很高的亲和力,体内自显影和免疫组化检测证实了这一点:研究结果强调了绿色纳米技术驱动的木瓜蛋白酶纳米颗粒作为通过 SPECT/CT 成像对乳腺和其他肿瘤进行分子成像的药物的潜力。这些结果标志着木瓜蛋白酶纳米颗粒作为诊断和治疗放射性核素载体的应用向前迈出了一大步,可将诊断/治疗有效载荷特异性地输送到肿瘤部位,从而开发出新一代纳米放射药物。
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引用次数: 0
Nano-Ayurvedic Medicine Approaches Using Ginkgo biloba-Phytochemicals Functionalized Gold Nanoparticles Against Breast Cancer. 利用银杏叶植物化学物质功能化金纳米粒子防治乳腺癌的纳米吠陀医学方法。
IF 4.9 Q2 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-09-23 eCollection Date: 2024-01-01 DOI: 10.2147/NSA.S478533
Velaphi C Thipe, Nya Hall, Amoolya Pandurangi, Samuel Ajayi, Prosper Emeh, Iti Gauttam, Rania Ghamgui, Fatima Hameedat, Sihem Khelil, Nhu Ky Ly, Mahmoud Salim, Anum Shahid Waleed, Prajna Hegde, Vrushali Hegde, Deepa Prakash, Ilaadevi Hegde, Kavita Katti, Alice Raphael Karikachery, Emilie Roger, Anne Landreau, Kattesh V Katti

Purpose: Breast cancer is a significant global health issue, contributing to 15% of cancer-related deaths. Our laboratory has pioneered a novel approach, combining Ayurvedic principles with green nanotechnology, to develop a scientifically rigorous medical modality referred to as Nano-Ayurvedic Medicine, recently approved by the US Patents and Trademarks Office. Here in we report a new Nano-Ayurvedic medicine agent derived from gold nanoparticles encapsulated with phytochemicals from Ginkgo biloba plant (GB-AuNPs).

Methods: We have developed biocompatible gold nanoparticles using electron-rich phytochemicals from Ginkgo biloba as reducing agent cocktail. Ginkgo biloba phytochemical-encapsulated gold nanoparticles (GB-AuNPs) were fully characterized, and their anticancer activity, including immunomodulatory profiles, were evaluated against breast (MDAMB-231) cancer cell lines.

Results: Characterization revealed spherical morphology for GB-AuNPs and possessed optimum in vitro stability through high zeta potential of -34 mV for optimum in vivo stability. The core size of GB-AuNPs of 19 nm allows for penetration into tumor cells through both EPR effects as well as through the receptor-mediated endocytosis. The Antitumor efficacy of this nano-ayurvedic medicine agent revealed strong antitumor effects of GB-AuNPs towards MDAMB-231. Our investigations reveal that GB-AuNPs enhance anti-tumor cytokines (IL-12, TNF-α, IFN-γ) and reduce pro-tumor cytokines (IL-10, IL-6), promoting the conversion of protumor M2 macrophages into M1-like macrophage antitumor phenotype. Cellular studies show that GB-AuNPs offer superior anti-tumor efficacy and a better safety profile against breast tumors compared to cisplatin.

Conclusion: Our investigations have demonstrated that the nano-ayurvedic medicine agent, GB-AuNPs, treats cancers through an immunomodulatory mechanism facilitated by elevated levels of anti-tumor cytokines (TNF-α, IFN-γ and IL-12) with concomitant downregulation of pro-tumor cytokines expression (IL-6 and IL-10). The green nanotechnology approach for the development of nano-ayurvedic medicine agent (GB-AuNPs), as described in this paper, presents new and attractive opportunities for treating human cancers and other debilitating diseases and disorders.

目的:乳腺癌是一个重大的全球健康问题,占癌症相关死亡人数的 15%。我们的实验室开创了一种新方法,将阿育吠陀原则与绿色纳米技术结合起来,开发出一种科学严谨的医疗模式,即纳米阿育吠陀医学,最近已获得美国专利和商标局的批准。在此,我们报告了一种新型纳米阿育吠陀药剂,该药剂由银杏叶植物化学物质包裹的金纳米粒子(GB-AuNPs)制成:我们利用银杏叶中富含电子的植物化学物质作为还原剂鸡尾酒,开发了生物相容性金纳米粒子。对银杏叶植物化学物质封装的金纳米粒子(GB-AuNPs)进行了全面表征,并评估了它们对乳腺癌(MDAMB-231)细胞系的抗癌活性,包括免疫调节特性:表征结果表明,GB-AuNPs呈球形,具有最佳的体外稳定性和-34 mV的高zeta电位,从而具有最佳的体内稳定性。GB-AuNPs 的核心尺寸为 19 nm,可通过 EPR 效应和受体介导的内吞作用穿透肿瘤细胞。这种纳米药剂的抗肿瘤功效表明,GB-AuNPs 对 MDAMB-231 有很强的抗肿瘤作用。我们的研究发现,GB-AuNPs 能增强抗肿瘤细胞因子(IL-12、TNF-α、IFN-γ),降低促肿瘤细胞因子(IL-10、IL-6),促进原肿瘤 M2 巨噬细胞向 M1 类巨噬细胞抗肿瘤表型转化。细胞研究表明,与顺铂相比,GB-AuNPs 对乳腺肿瘤具有更优越的抗肿瘤疗效和更好的安全性:我们的研究表明,纳米阿育吠陀药剂 GB-AuNPs 可通过免疫调节机制治疗癌症,该机制可促进抗肿瘤细胞因子(TNF-α、IFN-γ 和 IL-12)水平的升高,同时降低促肿瘤细胞因子(IL-6 和 IL-10)的表达。本文所述的开发纳米阿育吠陀药剂(GB-AuNPs)的绿色纳米技术方法为治疗人类癌症和其他衰弱性疾病和失调提供了新的、极具吸引力的机会。
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引用次数: 0
The Delivery of Mimic miRNA-7 into Glioblastoma Cells and Tumour Tissue by Graphene Oxide Nanosystems. 利用氧化石墨烯纳米系统向胶质母细胞瘤细胞和肿瘤组织输送模拟 miRNA-7。
IF 4.9 Q2 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-09-11 eCollection Date: 2024-01-01 DOI: 10.2147/NSA.S469193
Marta Kutwin, Malwina Sosnowska-Ławnicka, Barbara Nasiłowska, Agata Lange, Mateusz Wierzbicki, Sławomir Jaworski

Purpose: The use of nanotechnology in medicine has gained attention in developing drug delivery systems. GO has the potential to deliver microRNA (miRNA) mimics or antisense structures. MiRNAs regulate gene expression and their dysregulation is implicated in diseases, including cancer. This study aims to observe changes in morphology, viability, mRNA expression of mTOR/PI3K/Akt and PTEN genes in U87, U118, U251, A172 and T98 glioblastoma cells and xenograft models after GO self-assembly with mimic miRNA-7.

Methods: Colloidal suspension of graphene oxide (GO) was used for obtaining the GO-mimic miRNA-7 nanosystems by self-assembly method. The ultrastructure, size distribution and ATR-FTIR and UV-Vis spectrum were analyzed. The Zeta potential was measured to verify the stability of obtained nanosystem. The entrapment efficiency, loading capacity and released kinetics of mimic miRNA-7 form GO-mimic miRNA-7 nanosystems were analyzed. The transfection efficiency into the glioblastoma cell lines U87, U118, U251, A172 and T98 of mimic miRNA-7 delivered by GO nanosystems was measure by confocal microscopy and flow cytometry. The changes at mRNA expression level of mTOR, PI3K, AKT1 and PTEN genes was measured by qPCR analysis. The xenograft model of U87 and A172 tumour tissue was performed to analyze the effect at tumor size and volume after GO- mimic miRNA-7 nanosystem administration.

Results: The ultrastructure of GO-mimic miRNA-7 nanosystems showed high affinity of mimic miRNA into the GO. The results of transfection efficiency, cell morphology and viability showed that GO -miRNA-7 effectively deliver mimics miRNA-7 into U87, U118, U251, A172 and T98 glioblastoma cells. This approach can reverse miRNA-7 expression's downstream effects and target the mTOR PI3K/Akt pathway observed at gene expression level, reducing xenograft tumour size and volume.

Conclusion: The findings of the study could have significant implications for the development of advanced and precise GO based nanosystems specifically designed for miRNA therapy in cancer treatment.

目的:纳米技术在医学中的应用已在开发药物输送系统方面获得关注。GO 具有传递微小核糖核酸(miRNA)模拟物或反义结构的潜力。MiRNA 可调控基因表达,其失调与癌症等疾病有关。本研究旨在观察 U87、U118、U251、A172 和 T98 胶质母细胞瘤细胞和异种移植模型在 GO 与模拟 miRNA-7 自组装后的形态、活力、mTOR/PI3K/Akt 和 PTEN 基因的 mRNA 表达变化:方法:利用氧化石墨烯(GO)的胶体悬浮液,通过自组装方法获得GO模拟miRNA-7纳米系统。分析了纳米体系的超微结构、尺寸分布、ATR-FTIR 和 UV-Vis 光谱。测量了 Zeta 电位以验证所获得纳米系统的稳定性。分析了GO-mimic miRNA-7纳米系统对模拟miRNA-7的包埋效率、负载能力和释放动力学。共聚焦显微镜和流式细胞术测定了 GO 纳米系统向胶质母细胞瘤细胞系 U87、U118、U251、A172 和 T98 转染模拟 miRNA-7 的效率。通过 qPCR 分析测定了 mTOR、PI3K、AKT1 和 PTEN 基因 mRNA 表达水平的变化。对U87和A172肿瘤组织进行异种移植模型,分析GO-模拟miRNA-7纳米系统给药后对肿瘤大小和体积的影响:结果:GO-mimic miRNA-7纳米系统的超微结构显示mimic miRNA与GO有很高的亲和力。转染效率、细胞形态和活力结果表明,GO-miRNA-7 纳米系统能有效地将模拟 miRNA-7 导入 U87、U118、U251、A172 和 T98 胶质母细胞瘤细胞。这种方法可以逆转 miRNA-7 表达的下游效应,并在基因表达水平上靶向观察到的 mTOR PI3K/Akt 通路,减少异种移植肿瘤的大小和体积:结论:这项研究的发现对于开发基于 GO 的先进、精确的纳米系统,特别是用于治疗癌症的 miRNA 治疗具有重要意义。
{"title":"The Delivery of Mimic miRNA-7 into Glioblastoma Cells and Tumour Tissue by Graphene Oxide Nanosystems.","authors":"Marta Kutwin, Malwina Sosnowska-Ławnicka, Barbara Nasiłowska, Agata Lange, Mateusz Wierzbicki, Sławomir Jaworski","doi":"10.2147/NSA.S469193","DOIUrl":"https://doi.org/10.2147/NSA.S469193","url":null,"abstract":"<p><strong>Purpose: </strong>The use of nanotechnology in medicine has gained attention in developing drug delivery systems. GO has the potential to deliver microRNA (miRNA) mimics or antisense structures. MiRNAs regulate gene expression and their dysregulation is implicated in diseases, including cancer. This study aims to observe changes in morphology, viability, mRNA expression of mTOR/PI3K/Akt and PTEN genes in U87, U118, U251, A172 and T98 glioblastoma cells and xenograft models after GO self-assembly with mimic miRNA-7.</p><p><strong>Methods: </strong>Colloidal suspension of graphene oxide (GO) was used for obtaining the GO-mimic miRNA-7 nanosystems by self-assembly method. The ultrastructure, size distribution and ATR-FTIR and UV-Vis spectrum were analyzed. The Zeta potential was measured to verify the stability of obtained nanosystem. The entrapment efficiency, loading capacity and released kinetics of mimic miRNA-7 form GO-mimic miRNA-7 nanosystems were analyzed. The transfection efficiency into the glioblastoma cell lines U87, U118, U251, A172 and T98 of mimic miRNA-7 delivered by GO nanosystems was measure by confocal microscopy and flow cytometry. The changes at mRNA expression level of <i>mTOR, PI3K, AKT1</i> and <i>PTEN</i> genes was measured by qPCR analysis. The xenograft model of U87 and A172 tumour tissue was performed to analyze the effect at tumor size and volume after GO- mimic miRNA-7 nanosystem administration.</p><p><strong>Results: </strong>The ultrastructure of GO-mimic miRNA-7 nanosystems showed high affinity of mimic miRNA into the GO. The results of transfection efficiency, cell morphology and viability showed that GO -miRNA-7 effectively deliver mimics miRNA-7 into U87, U118, U251, A172 and T98 glioblastoma cells. This approach can reverse miRNA-7 expression's downstream effects and target the mTOR PI3K/Akt pathway observed at gene expression level, reducing xenograft tumour size and volume.</p><p><strong>Conclusion: </strong>The findings of the study could have significant implications for the development of advanced and precise GO based nanosystems specifically designed for miRNA therapy in cancer treatment.</p>","PeriodicalId":18881,"journal":{"name":"Nanotechnology, Science and Applications","volume":"17 ","pages":"167-188"},"PeriodicalIF":4.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antibacterial, Antibiofilm, and Tooth Color Preservation Capacity of Magnesium Oxide Nanoparticles Varnish (in vitro Study). 氧化镁纳米粒子涂膜的抗菌、抗生物膜和牙齿保色能力(体外研究)。
IF 4.9 Q2 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-06-27 eCollection Date: 2024-01-01 DOI: 10.2147/NSA.S462771
Sonya Jamal Hamalaw, Fadil Abdulla Kareem, Arass Jalal Noori

Purpose: Antibacterial and antibiofilm properties of magnesium oxide nanoparticles (MgONPs) mixture assessed against Streptococcus mutans (S. mutans), in addition to examining MgONPs varnish impact on the preservation of the tooth color and inhibition of methylene blue diffusion to the enamel.

Methods: MgONPs mixture was prepared in deionized water (DW), absolute ethanol (E), and rosin with ethanol (RE), named varnish. The antibacterial and antibiofilm capacities of MgONPs mixtures were tested by agar well diffusion, colony-forming unit (CFU), and biofilm inhibition microtiter methods in triplicate and compared to sodium fluoride varnish (NaF) and chlorhexidine mouthwash (ChX). A spectrophotometer was used to record basic tooth color. The artificial demineralization was initiated for 96 h. Then, experimental materials were applied to the corresponding group, and 10-day pH cycles proceeded. Then, the color was recorded in the same ambient environment. The methylene blue diffusion was evaluated by staining the samples for 24 h. After that, the diffusion test was calculated by a digital camera attached to the stereomicroscope.

Results: The agar well diffusion test expressed a significant inhibition zone with all MgONPs mixtures (p = 0.000), and maximum inhibition zone diameter associated with MgONPs-RE. The same finding was observed in the CFU test. Additionally, 2.5%, 5%, and 10% MgONPs-RE varnish showed strong biofilm inhibition capacity (p = 0.039) compared to NaF and ChX groups that inhibit biofilm formation moderately (p = 0.003). The study shows that the 5% MgONPs-RE varnish maintains basic tooth color with minimal methylene blue diffusion compared to NaF varnish (p = 0.00).

Conclusion: Evaluating MgONPs as a mixture revealed antibacterial and antibiofilm capacity against S. mutans with a higher effect of MgONPs-RE varnish. Also, examining the topical effect of MgONPs-RE varnish on the preservation of the tooth color after pH cycle challenges and methylene blue diffusion to enamel confirmed the high performance of MgONPs-RE varnish at 5%.

目的:评估氧化镁纳米粒子(MgONPs)混合物对变异链球菌(S. mutans)的抗菌和抗生物膜特性,此外还研究 MgONPs 光油对保持牙齿颜色和抑制亚甲蓝向珐琅质扩散的影响:方法:在去离子水(DW)、绝对乙醇(E)和含乙醇的松香(RE)中制备 MgONPs 混合物,命名为清漆。采用琼脂井扩散法、菌落形成单位法和生物膜抑制微滴定法测试了 MgONPs 混合物的抗菌和抗生物膜能力,一式三份,并与氟化钠清漆(NaF)和洗必泰漱口水(ChX)进行了比较。使用分光光度计记录牙齿的基本颜色。然后将实验材料涂抹在相应的组别上,进行为期 10 天的 pH 循环。然后,在相同的环境中记录牙色。将样品染色 24 小时,评估亚甲基蓝扩散情况:结果:琼脂井扩散试验表明,所有 MgONPs 混合物都有明显的抑制区(p = 0.000),MgONPs-RE 的抑制区直径最大。在 CFU 试验中也观察到了同样的结果。此外,与 NaF 和 ChX 组相比,2.5%、5% 和 10%的 MgONPs-RE 清漆显示出很强的生物膜抑制能力(p = 0.039),而 NaF 和 ChX 组对生物膜形成的抑制作用一般(p = 0.003)。研究表明,与 NaF 光油相比,5% MgONPs-RE 光油可保持基本牙色,亚甲蓝扩散极小(p = 0.00):将 MgONPs 作为混合物进行评估后发现,MgONPs-RE 上光剂具有更强的抗菌和抗生物膜能力。此外,通过研究 MgONPs-RE 清漆在 pH 循环挑战和亚甲蓝向珐琅质扩散后对牙齿颜色保持的局部效果,证实了 5% 的 MgONPs-RE 清漆具有很高的性能。
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引用次数: 0
Evaluation of the Antimicrobial, Cytotoxic, and Physical Properties of Selected Nano-Complexes in Bovine Udder Inflammatory Pathogen Control. 评估选定纳米复合物在牛乳房炎症病原体控制中的抗菌性、细胞毒性和物理特性。
IF 4.9 Q1 Engineering Pub Date : 2024-03-20 eCollection Date: 2024-01-01 DOI: 10.2147/NSA.S447810
Mateusz Wierzbicki, Magdalena Kot, Agata Lange, Aleksandra Kalińska, Marcin Gołębiewski, Sławomir Jaworski

Purpose: Mastitis in dairy cows is a worldwide problem faced by dairy producers. Treatment mainly involves antibiotic therapy, however, due to widespread antibiotic resistance among bacteria, such treatments are no longer effective. For this reason, scientists are searching for new solutions to combat mastitis, which is caused by bacteria, fungi, and algae. One of the most promising solutions, nanotechnology, is attracting research due to its biocidal properties. The purpose of this research was to determine the biocidal properties of nanocomposites as a potential alternative to antibiotics in the control of mastitis, as well as to determine whether the use of nanoparticles and what concentration is safe for the breeder and the animal.

Patients and methods: In this study, the effects of Ag, Au, Cu, Fe, and Pt nanoparticles and their complexes were evaluated in relation to the survival of bacteria and fungi isolated from cattle diagnosed with mastitis, their physicochemical properties, and their toxicity to bovine and human mammary epithelial cells BME-UV1 and HMEC (human microvascular endothelial cells). Moreover, E. coli, S. aureus, C. albicans, and Prototheca sp. invasion was assessed using the alginate bead (bioprinted) model. The NPs were tested at concentrations of 25, 12.5, 6.25, 3.125, 1.56 mg/l for Au, Ag, Cu and Fe NPs, and 10, 5, 2.5, 1.25, 0.625 mg/l for Pt.

Results: With the exception of Fe and Pt, all exhibited biocidal properties against isolates, while the AgCu complex had the best effect. In addition, nanoparticles showed synergistic effects, while the low concentrations had no toxic effect on BME-UV1 and HMEC cells.

Conclusion: Synergistic effects of nanoparticles and no toxicity to bovine and human cells might, in the future, be an effective alternative in the fight against microorganisms responsible for mastitis, and the implementation of research results in practice would reduce the percentage of dairy cows suffering from mastitis. The problem of increasing antibiotic resistance is posing a global threat to human's and animal's health, and requires comprehensive research to evaluate the potential use of nanoparticles - especially their complexes - as well as to determine whether nanoparticles are safe for the breeders and the animals. The conducted series of studies allows further consideration of the use of the obtained results in practice, creating a potentially new alternative to antibiotics in the treatment and prevention of mastitis in dairy cattle.

目的:奶牛乳腺炎是奶制品生产商面临的一个世界性问题。治疗方法主要包括抗生素疗法,然而,由于细菌普遍对抗生素产生抗药性,这种疗法已不再有效。因此,科学家们正在寻找新的解决方案来防治由细菌、真菌和藻类引起的乳腺炎。最有前途的解决方案之一--纳米技术因其杀菌特性而备受研究关注。本研究的目的是确定纳米复合材料的杀菌特性,以此作为抗生素在控制乳腺炎方面的潜在替代品,同时确定纳米颗粒的使用和浓度对饲养者和动物是否安全:本研究评估了Ag、Au、Cu、Fe和Pt纳米颗粒及其复合物对从诊断为乳腺炎的牛身上分离出的细菌和真菌的存活率、理化性质以及对牛和人乳腺上皮细胞BME-UV1和HMEC(人微血管内皮细胞)的毒性的影响。此外,还使用藻酸盐珠(生物打印)模型评估了大肠杆菌、金黄色葡萄球菌、白僵菌和原生动物的侵袭情况。金、银、铜和铁 NPs 的测试浓度分别为 25、12.5、6.25、3.125 和 1.56 毫克/升,铂的测试浓度分别为 10、5、2.5、1.25 和 0.625 毫克/升:结果:除铁和铂外,其他纳米粒子都具有杀灭分离菌的特性,而银铜复合物的效果最好。此外,纳米粒子还显示出协同效应,而低浓度纳米粒子对 BME-UV1 和 HMEC 细胞没有毒性作用:纳米粒子具有协同效应,对牛和人体细胞无毒性,未来可能成为对抗乳腺炎微生物的有效替代品,将研究成果应用于实践将降低奶牛患乳腺炎的比例。抗生素耐药性不断增加的问题正在对人类和动物的健康构成全球性威胁,因此需要进行全面研究,以评估纳米颗粒(尤其是其复合物)的潜在用途,并确定纳米颗粒对饲养者和动物是否安全。通过开展一系列研究,可以进一步考虑在实践中使用所取得的成果,从而在治疗和预防奶牛乳腺炎方面创造出一种可能替代抗生素的新方法。
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引用次数: 0
Antihistamine and Wound Healing Potential of Gold Nanoparticles Synthesized Using Bulbine frutescens (L.) Willd. 使用 Bulbine frutescens (L.) Willd.合成的金纳米粒子的抗组胺和伤口愈合潜力
IF 4.9 Q1 Engineering Pub Date : 2024-03-13 eCollection Date: 2024-01-01 DOI: 10.2147/NSA.S445116
Marizé Cuyler, Danielle Twilley, Velaphi C Thipe, Vusani Mandiwana, Michel L Kalombo, Suprakas S Ray, Rirhandzu Shamaine Rikhotso-Mbungela, Arno Janse van Vuuren, Will Coetsee, Kattesh V Katti, Namrita Lall

Background: Atopic dermatitis (eczema) is an inflammatory skin condition with synthetic treatments that induce adverse effects and are ineffective. One of the proposed causes for the development of the condition is the outside-in hypothesis, which states that eczema is caused by a disruption in the skin barrier. These disruptions include developing dry cracked skin, which promotes the production of histamine. Bulbine frutescens (BF) is traditionally used to treat wounds and eczema; however, limited research has been conducted to scientifically validate this. Furthermore, gold nanoparticles (AuNPs) have been used to repair damaged skin; however, no research has been conducted on AuNPs synthesized using BF.

Purpose: The study aimed to determine whether BF alleviated skin damage through wound healing, reducing the production of histamine and investigate whether AuNPs synthesized using BF would enhance biological activity.

Methods: Four extracts and four synthesized AuNPs were prepared using BF and their antiproliferative and wound healing properties against human keratinocyte cells (HaCaT) were evaluated. Thereafter, the selected samples antiproliferative activity and antihistamine activity against phorbol 12-myristate 13-acetate (PMA) stimulated granulocytes were evaluated.

Results: Of the eight samples, the freeze-dried leaf juice (BFE; p < 0.01) extract and its AuNPs (BFEAuNPs; p < 0.05) displayed significant wound closure at 100 µg/mL and were further evaluated. The selected samples displayed a fifty percent inhibitory concentration (IC50) of >200 µg/mL against PMA stimulated granulocytes. Compared to the untreated (media with PMA) control (0.30 ± 0.02 ng/mL), BFEAuNPs significantly inhibited histamine production at a concentration of 100 (p < 0.01) and 50 µg/mL (p < 0.001).

Conclusion: BFE and BFEAuNPs stimulated wound closure, while BFEAuNPs significantly inhibited histamine production. Further investigation into BFEAuNPs in vivo wound healing activity and whether it can target histamine-associated receptors on mast cells as a potential mechanism of action should be considered.

背景:特应性皮炎(湿疹)是一种炎症性皮肤病,人工合成的治疗方法会引起不良反应且效果不佳。该假说认为,湿疹是由皮肤屏障破坏引起的。这些破坏包括皮肤干裂,从而促进组胺的产生。Bulbine frutescens(BF)传统上被用于治疗伤口和湿疹;然而,对其进行科学验证的研究还很有限。此外,金纳米粒子(AuNPs)已被用于修复受损皮肤;然而,目前还没有关于使用 BF 合成的 AuNPs 的研究。研究目的:本研究旨在确定 BF 是否能通过伤口愈合减轻皮肤损伤,减少组胺的产生,并调查使用 BF 合成的 AuNPs 是否会增强生物活性:方法: 使用 BF 制备了四种提取物和四种合成的 AuNPs,并评估了它们对人角质细胞(HaCaT)的抗增殖性和伤口愈合性。随后,对所选样品的抗增殖活性和抗组胺活性进行了评估:结果:在八种样品中,冻干叶汁(BFE;p < 0.01)提取物及其 AuNPs(BFEAuNPs;p < 0.05)在 100 µg/mL 的浓度下显示出明显的伤口闭合效果,并被进一步评估。所选样品对 PMA 刺激的粒细胞的抑制浓度(IC50)大于 200 µg/mL。与未经处理(含有 PMA 的培养基)的对照组(0.30 ± 0.02 ng/mL)相比,BFEAuNPs 在浓度为 100 微克/毫升(p < 0.01)和 50 微克/毫升(p < 0.001)时可显著抑制组胺的产生:结论:BFE 和 BFEAuNPs 能刺激伤口闭合,而 BFEAuNPs 能明显抑制组胺的产生。应考虑进一步研究 BFEAuNPs 在体内的伤口愈合活性,以及它是否能将肥大细胞上的组胺相关受体作为潜在的作用机制。
{"title":"Antihistamine and Wound Healing Potential of Gold Nanoparticles Synthesized Using <i>Bulbine frutescens</i> (L.) Willd.","authors":"Marizé Cuyler, Danielle Twilley, Velaphi C Thipe, Vusani Mandiwana, Michel L Kalombo, Suprakas S Ray, Rirhandzu Shamaine Rikhotso-Mbungela, Arno Janse van Vuuren, Will Coetsee, Kattesh V Katti, Namrita Lall","doi":"10.2147/NSA.S445116","DOIUrl":"https://doi.org/10.2147/NSA.S445116","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (eczema) is an inflammatory skin condition with synthetic treatments that induce adverse effects and are ineffective. One of the proposed causes for the development of the condition is the outside-in hypothesis, which states that eczema is caused by a disruption in the skin barrier. These disruptions include developing dry cracked skin, which promotes the production of histamine. <i>Bulbine frutescens</i> (BF) is traditionally used to treat wounds and eczema; however, limited research has been conducted to scientifically validate this. Furthermore, gold nanoparticles (AuNPs) have been used to repair damaged skin; however, no research has been conducted on AuNPs synthesized using BF.</p><p><strong>Purpose: </strong>The study aimed to determine whether BF alleviated skin damage through wound healing, reducing the production of histamine and investigate whether AuNPs synthesized using BF would enhance biological activity.</p><p><strong>Methods: </strong>Four extracts and four synthesized AuNPs were prepared using BF and their antiproliferative and wound healing properties against human keratinocyte cells (HaCaT) were evaluated. Thereafter, the selected samples antiproliferative activity and antihistamine activity against phorbol 12-myristate 13-acetate (PMA) stimulated granulocytes were evaluated.</p><p><strong>Results: </strong>Of the eight samples, the freeze-dried leaf juice (BFE; <i>p</i> < 0.01) extract and its AuNPs (BFEAuNPs; <i>p</i> < 0.05) displayed significant wound closure at 100 µg/mL and were further evaluated. The selected samples displayed a fifty percent inhibitory concentration (IC<sub>50</sub>) of >200 µg/mL against PMA stimulated granulocytes. Compared to the untreated (media with PMA) control (0.30 ± 0.02 ng/mL), BFEAuNPs significantly inhibited histamine production at a concentration of 100 (<i>p</i> < 0.01) and 50 µg/mL (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>BFE and BFEAuNPs stimulated wound closure, while BFEAuNPs significantly inhibited histamine production. Further investigation into BFEAuNPs in vivo wound healing activity and whether it can target histamine-associated receptors on mast cells as a potential mechanism of action should be considered.</p>","PeriodicalId":18881,"journal":{"name":"Nanotechnology, Science and Applications","volume":"17 ","pages":"59-76"},"PeriodicalIF":4.9,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10949377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Chemical Modification to Improve Solubility of Chitosan and Its Derivatives Application, Preparation Method, Toxicity as a Nanoparticles. 提高壳聚糖及其衍生物溶解度的化学修饰 作为纳米粒子的应用、制备方法和毒性。
IF 4.9 Q1 Engineering Pub Date : 2024-03-07 eCollection Date: 2024-01-01 DOI: 10.2147/NSA.S450026
Suryani Suryani, Anis Yohana Chaerunisaa, I Made Joni, Ruslin Ruslin, Vica Aspadiah, Anton Anton, Ari Sartinah, La Ode Ahmad Nur Ramadhan

Chitosan is a functional polymer in the pharmaceutical field, including for nanoparticle drug delivery systems. Chitosan-based nanoparticles are a promising carrier for a wide range of therapeutic agents and can be administered in various routes. Solubility is the main problem for its production and utilization in large-scale industries. Chitosan modifications have been employed to enhance its solubility, including chemical modification. Many reviews have reported the chemical modification but have not focused on the specific characteristics obtained. This review focused on the modification to improve chitosan solubility. Additionally, this review also focused on the application of chitosan derivatives in nanoparticle drug delivery systems since very few similar reviews have been reported. The specific method for chitosan derivative-based nanoparticles was also reported and the latest report of chitosan, chitosan derivative, and chitosan toxicity were also described.

壳聚糖是制药领域的一种功能性聚合物,可用于纳米颗粒给药系统。以壳聚糖为基础的纳米粒子是一种前景广阔的载体,可用于多种治疗药物的给药途径。溶解性是其大规模生产和使用的主要问题。为了提高壳聚糖的可溶性,人们对其进行了化学改性等改良。许多综述都报道了化学改性的情况,但并未关注所获得的具体特性。这篇综述主要介绍了提高壳聚糖溶解度的改性方法。此外,本综述还关注壳聚糖衍生物在纳米颗粒给药系统中的应用,因为很少有类似的综述报道。此外,还介绍了基于壳聚糖衍生物的纳米粒子的具体制备方法,以及壳聚糖、壳聚糖衍生物和壳聚糖毒性的最新报道。
{"title":"The Chemical Modification to Improve Solubility of Chitosan and Its Derivatives Application, Preparation Method, Toxicity as a Nanoparticles.","authors":"Suryani Suryani, Anis Yohana Chaerunisaa, I Made Joni, Ruslin Ruslin, Vica Aspadiah, Anton Anton, Ari Sartinah, La Ode Ahmad Nur Ramadhan","doi":"10.2147/NSA.S450026","DOIUrl":"10.2147/NSA.S450026","url":null,"abstract":"<p><p>Chitosan is a functional polymer in the pharmaceutical field, including for nanoparticle drug delivery systems. Chitosan-based nanoparticles are a promising carrier for a wide range of therapeutic agents and can be administered in various routes. Solubility is the main problem for its production and utilization in large-scale industries. Chitosan modifications have been employed to enhance its solubility, including chemical modification. Many reviews have reported the chemical modification but have not focused on the specific characteristics obtained. This review focused on the modification to improve chitosan solubility. Additionally, this review also focused on the application of chitosan derivatives in nanoparticle drug delivery systems since very few similar reviews have been reported. The specific method for chitosan derivative-based nanoparticles was also reported and the latest report of chitosan, chitosan derivative, and chitosan toxicity were also described.</p>","PeriodicalId":18881,"journal":{"name":"Nanotechnology, Science and Applications","volume":"17 ","pages":"41-57"},"PeriodicalIF":4.9,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10926861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Factors Affecting the Synthesis of Bovine Serum Albumin Nanoparticles Using the Desolvation Method. 用脱溶法合成牛血清白蛋白纳米颗粒的影响因素。
IF 4.9 Q1 Engineering Pub Date : 2024-01-31 eCollection Date: 2024-01-01 DOI: 10.2147/NSA.S441324
Yenni Puspita Tanjung, Mayang Kusuma Dewi, Vesara Ardhe Gatera, Melisa Intan Barliana, I Made Joni, Anis Yohana Chaerunisaa

Currently, protein-based nanoparticles are in high demand as drug delivery systems due to their exceptional qualities, including nontoxicity, nonantigenicity, and biodegradability. Other qualities include high nutritional value, abundance of renewable resources, excellent drug binding capacity, greater stability during storage and in vivo, as well as ease of upgrading during manufacture. Examples of protein suitable for this purpose include ovalbumin (OVA) derived from egg white, human serum albumin (HSA), and bovine serum albumin (BSA). To create albumin nanoparticles, six different processes have been investigated in depth and are frequently used in drug delivery systems. These included desolvation, thermal gelation, emulsification, NAB technology, self-assembly, and nanospray drying. Several experimental conditions in the synthesis of albumin nanoparticles can affect the physicochemical characterization. Therefore, this study aimed to provide an overview of various experimental conditions capable of affecting the physicochemical characteristics of BSA nanoparticles formed using the desolvation method. By considering the variation in optimal experimental conditions, a delivery system of BSA nanoparticles with the best physicochemical characterization results could be developed.

目前,以蛋白质为基础的纳米粒子因其无毒性、无抗原性和生物降解性等优异品质而成为需求量很大的药物输送系统。其他特性还包括营养价值高、可再生资源丰富、药物结合能力强、在储存和体内更稳定,以及在制造过程中易于升级。适用于这一目的的蛋白质包括从蛋清中提取的卵清蛋白(OVA)、人血清白蛋白(HSA)和牛血清白蛋白(BSA)。为了制造白蛋白纳米粒子,已经对六种不同的工艺进行了深入研究,这些工艺经常用于药物输送系统。这些工艺包括脱溶、热凝胶化、乳化、NAB 技术、自组装和纳米喷雾干燥。白蛋白纳米颗粒合成过程中的一些实验条件会影响其理化特性。因此,本研究旨在概述能够影响使用去溶胶法形成的白蛋白纳米粒子理化特性的各种实验条件。通过考虑最佳实验条件的变化,可以开发出一种具有最佳理化表征结果的 BSA 纳米粒子输送系统。
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引用次数: 0
Formulation and Characterization of Intranasal Drug Delivery of Frovatriptan-Loaded Binary Ethosomes Gel for Brain Targeting. 用于脑靶向的弗罗阿曲普坦二元乙素体凝胶的鼻内给药配方与表征
IF 4.9 Q2 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-01-16 eCollection Date: 2024-01-01 DOI: 10.2147/NSA.S442951
Mohammed Layth Hamzah, Hanan Jalal Kassab

Background: Frovatriptan succinate (FVT) is an effective medication used to treat migraines; however, available oral formulations suffer from low permeability; accordingly, several formulations of FVT were prepared.

Objective: Prepare, optimize, and evaluate FVT-BE formulation to develop enhanced intranasal binary nano-ethosome gel.‎.

Methods: Binary ethosomes were prepared using different concentrations of phospholipid PLH90, ethanol, propylene glycol, and cholesterol by thin film hydration and characterized by particle size, zeta potential, and entrapment efficiency. Furthermore, in-vitro, in-vivo, ex-vivo, pharmacokinetics, and histopathological studies were done.

Results: Regarding FVT-loaded BE, formula (F9) demonstrated the best parameters from the other formulas; with the lowest particle size (154.1±4.38‎ nm), lowest PDI (‎0.213±0.05), highest zeta potential (‎-46.94±1.05), and highest entrapment efficiency (89.34±2.37%). Regarding gel formulation, G2 showed the best gel formula with drug content (‎99.82±0.02‎%) and spreadability (12.88 g/cm2). In-vitro study results showed that, in the first 30 minutes, around 22.3% of the medication is released, whereas, after 24 hours, about 98.56% is released in G2.

Conclusion: Based on enhancing the bioavailability and sustaining the drug release, it can be concluded that the Frovatriptan-Loaded Binary ethosome Gel as nano-delivery was developed as a promising non-invasive drug delivery system for treating migraine.

背景:琥珀酸氟伐曲普坦(FVT)是一种治疗偏头痛的有效药物;然而,现有的口服制剂存在渗透性低的问题;因此,制备了几种FVT制剂:制备、优化和评估 FVT-BE 配方,以开发增强型鼻内二元纳米乙素体凝胶:方法:使用不同浓度的磷脂 PLH90、乙醇、丙二醇和胆固醇,通过薄膜水合法制备二元乙硫体,并通过粒度、ZETA电位和夹持效率对其进行表征。此外,还进行了体外、体内、体外、药代动力学和组织病理学研究:在负载 FVT 的 BE 方面,配方(F9)的参数是其他配方中最好的;粒度最小(154.1±4.38 nm),PDI 最低(0.213±0.05),zeta 电位最高(-46.94±1.05),包埋效率最高(89.34±2.37%)。在凝胶配方方面,G2 的药物含量(99.82±0.02%)和铺展性(12.88 g/cm2)均为最佳。体外研究结果表明,在最初的 30 分钟内,约有 22.3% 的药物被释放出来,而在 24 小时后,G2 中约有 98.56% 的药物被释放出来:基于提高生物利用度和维持药物释放的原理,可以得出结论:弗罗阿曲普坦负载二元乙素体凝胶作为纳米给药,是一种治疗偏头痛的前景广阔的非侵入性给药系统。
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引用次数: 0
Silver Shell Thickness-Dependent Conductivity of Coatings Based on Ni@Ag Core@shell Nanoparticles. 基于 Ni@Ag Core@shell 纳米粒子的涂层的导电性取决于银壳厚度。
IF 4.9 Q1 Engineering Pub Date : 2023-12-27 eCollection Date: 2023-01-01 DOI: 10.2147/NSA.S435432
Anna Pajor-Świerzy, Katarzyna Kozak, Dorota Duraczyńska, Agata Wiertel-Pochopień, Jan Zawała, Krzysztof Szczepanowicz

Introductions: Ink based on metallic nanoparticles has been widely used so far for the fabrication of electronic circuits and devices using printing technology. This study aimed at the analysis of the effect of the silver shell thickness of nickel@silver core@shell (Ni@Ag) nanoparticles (NPs) on the fabrication and conductive properties of deposited coatings.

Methods: The process of the synthesis of Ni@Ag NPs with various silver shell thicknesses was developed. The physicochemical properties (size, stability against aggregation process) of synthesized Ni@Ag nanoparticles were analyzed. The films based on ink containing Ni@Ag NPs with different silver shell thicknesses were fabricated and sintered in a temperature range of 120-300 °C and at times from 15 to 90 min. The dependence of their conductive properties on the applied temperature and time as well as silver shell thickness was evaluated.

Results: Ni NPs were coated with 10, 20, 30, 35, 45, and 55 nm silver shell thickness. The resistivity of coatings based on obtained NPs depends on the thickness of the Ag shell and the sintering temperature. After sintering at 300 °C, the highest decrease in its value (at an optimal sintering time of 60 min) from about 100 µΩ·cm to 9 µΩ·cm was observed when the thickness of the shell increased from 10 to 55 nm. At the lowest sintering temperature (120 °C) the highest conductivity (about 50% of that for bulk nickel) was obtained for films based on Ni@Ag NPs with 45 and 55 nm of the silver shell thickness.

Discussions: The analysis of the resistivity of the sintered films showed that higher conductivity was obtained for the coatings formed from Ni@Ag NPs with the thicker Ag shell; moreover, thicker shells allowed a lowering of sintering temperature due to higher conductivity and a lower melting point of silver in comparison to nickel NPs.

介绍:迄今为止,基于金属纳米颗粒的油墨已被广泛用于利用印刷技术制造电子电路和器件。本研究旨在分析镍@银核@壳(Ni@Ag)纳米粒子(NPs)银壳厚度对沉积涂层的制造和导电性能的影响:方法:建立了不同银壳厚度的 Ni@Ag NPs 的合成工艺。分析了合成的 Ni@Ag 纳米粒子的理化性质(尺寸、对聚集过程的稳定性)。以含有不同银壳厚度的 Ni@Ag NPs 墨水为基础制作了薄膜,并在 120-300 °C 的温度范围和 15 至 90 分钟的时间内进行了烧结。评估了其导电性能与应用温度、时间以及银壳厚度的关系:结果:Ni NPs 的银壳厚度分别为 10、20、30、35、45 和 55 nm。所获得的 NPs 涂层的电阻率取决于银壳厚度和烧结温度。在 300 °C 下烧结后,当银壳厚度从 10 纳米增加到 55 纳米时,电阻率值从约 100 µΩ-cm 降至 9 µΩ-cm,降幅最大(最佳烧结时间为 60 分钟)。在最低烧结温度(120 °C)下,银壳厚度为 45 和 55 nm 的 Ni@Ag NPs 薄膜的导电率最高(约为块状镍导电率的 50%):烧结薄膜的电阻率分析表明,银壳较厚的 Ni@Ag NPs 所形成的镀层具有更高的导电率;此外,与镍 NPs 相比,银壳较厚的镀层具有更高的导电率和更低的熔点,因此可以降低烧结温度。
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Nanotechnology, Science and Applications
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