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Penetration Enhancer-Free Mixed Micelles for Improving Eprinomectin Transdermal c Efficiency in Animal Parasitic Infections Therapy. 用于提高动物寄生虫感染治疗中艾普罗米星经皮 c 效率的无穿透增强剂混合胶束
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/IJN.S476164
Yujuan Mao, Tianjiao Hao, Hongxiu Zhang, Xiaofei Gu, Jing Wang, Feifei Shi, Xiaolan Chen, Liuna Guo, Jie Gao, Yan Shen, JinLin Zhang, Shenglan Yu

Introduction: Eprinomectin offers promise against parasitic infections. This study develops Eprinomectin (EPR) mixed micelles for transdermal delivery, aiming to enhance efficacy and convenience against endoparasites and ectoparasites. Physicochemical characterization and pharmacokinetic studies were conducted to assess its potential as an effective treatment for parasitic infections.

Methods: Blank and EPR mixed micelles were prepared using PEG-40 Hydrogenated castor oil (RH-40) and Nonyl phenol polyoxyethylene ether 40 (NP-40). Critical micelle concentrations (CMC) determined using the pyrene fluorescence probe method. Particle size, EE, DL, in vitro release, permeation, and skin irritation were evaluated. In vivo pharmacokinetic studies were conducted in male Sprague-Dawley rats.

Results: Results show that EPR mixed micelles present suitable stability, physicochemical properties, and safety. Moreover, the rapid release and high bioavailability of EPR mixed micelles have also been verified in the study. Pharmacokinetic experiments in vivo showed that an improvement in the transdermal absorption and bioavailability of EPR after encapsulation in mixed micelles formulations.

Conclusion: The results proved that the novel mixed micelles are safe and effective and are expected to become a promising veterinary nano-delivery system.

介绍:埃普瑞诺米星有望防治寄生虫感染。本研究开发了用于透皮给药的埃普瑞诺米星(EPR)混合胶束,旨在提高对内寄生虫和外寄生虫的疗效和便利性。研究人员进行了理化表征和药代动力学研究,以评估其作为寄生虫感染有效治疗方法的潜力:使用 PEG-40 氢化蓖麻油(RH-40)和壬基酚聚氧乙烯醚 40(NP-40)制备空白胶束和 EPR 混合胶束。使用芘荧光探针法测定临界胶束浓度(CMC)。对粒度、EE、DL、体外释放、渗透性和皮肤刺激性进行了评估。在雄性 Sprague-Dawley 大鼠体内进行了药代动力学研究:结果表明,EPR 混合胶束具有合适的稳定性、理化性质和安全性。此外,EPR 混合胶束的快速释放和高生物利用度也在研究中得到了验证。体内药代动力学实验表明,EPR 被混合胶束制剂包裹后,其透皮吸收和生物利用率均有所提高:结果证明,新型混合胶束安全有效,有望成为一种前景广阔的兽药纳米给药系统。
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引用次数: 0
Enhanced Bacterial and Biofilm Adhesion Resistance of ALD Nano-TiO2 Coatings Compared to AO Coatings on Titanium Abutments. 与钛基台上的 AO 涂层相比,ALD 纳米二氧化钛涂层具有更强的抗细菌和生物膜粘附性。
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/IJN.S482478
Yu Pan, Lili Cao, Libing Chen, Linjuan Gao, Xia Wei, Honglei Lin, Lei Jiang, Yinghui Wang, Hui Cheng

Purpose: The study was intended to compare the surface properties and the bacterial and biofilm adhesion resistance of two potential antibacterial nanometer titanium dioxide (nano-TiO2) coatings on dental titanium (Ti) abutments prepared by atomic layer deposition (ALD) and the anodic oxidation (AO) techniques.

Methods: Nano-TiO₂ coatings were developed using ALD and AO techniques and applied to Ti surfaces. The surface properties and the bacterial and biofilm adhesion resistance of these coatings were evaluated against commonly used Ti and Zirconia (ZrO₂) surfaces. The chemical compositions, crystalline forms, surface topography, roughness and hydrophilicity were characterized. The antibacterial performance was assessed by the scanning electron microscope (SEM), the Colony-forming unit (CFU) assay and the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay using in vitro models of Staphylococcus aureus (S. aureus), Streptococcus mutans (S. mutans), and Porphyromonas gingivalis (P. gingivalis) in both single- and mixed-species bacterial compositions.

Results: ALD-prepared nano-TiO₂ coatings resulted in a dense, smooth, and less hydrophilic surface with an anatase phase, significantly reducing the adhesion of the three bacteria by over 50%, comparable to ZrO₂. In contrast, AO-prepared coatings led to a less hydrophilic surface, characterized by various nano-sized pores within the oxide film. This alteration, however, had no impact on the adhesion of the three bacteria. The adhesion patterns for mixed-species bacteria were generally consistent with single-species results.

Conclusion: ALD-prepared nano-TiO₂ coatings on Ti abutments demonstrated promising antibacterial properties comparable to ZrO₂ surfaces, suggesting potential in preventing peri-implantitis. However, the bacterial and biofilm adhesion resistance of AO-produced nano-TiO₂ coatings was limited.

目的:本研究旨在比较通过原子层沉积(ALD)和阳极氧化(AO)技术制备的两种潜在抗菌纳米二氧化钛(Nano-TiO2)涂层在牙科钛(Ti)基台上的表面特性以及抗细菌和生物膜附着性:方法:采用原子层沉积(ALD)和阳极氧化(AO)技术制备了纳米二氧化钛涂层,并将其应用于钛基台表面。对照常用的钛和氧化锆(ZrO₂)表面,对这些涂层的表面特性以及抗细菌和生物膜附着性进行了评估。对涂层的化学成分、结晶形式、表面形貌、粗糙度和亲水性进行了表征。通过扫描电子显微镜(SEM)、菌落形成单位(CFU)检测法和 3-(4,5-二甲基噻唑基-2)-2,5-二苯基溴化四氮唑(MTT)检测法,使用金黄色葡萄球菌(S.金黄色葡萄球菌(S. aureus)、变异链球菌(S. mutans)和牙龈卟啉单胞菌(P. gingivalis)在单一菌种和混合菌种组成中的体外模型进行测定:结果:ALD 制备的纳米氧化钛涂层表面致密、光滑、亲水性较低且具有锐钛矿相,可显著降低这三种细菌 50%以上的粘附性,与氧化锆相当。相比之下,AO 制备的涂层表面亲水性较差,氧化膜中存在各种纳米级孔隙。不过,这种变化对三种细菌的附着力没有影响。混合菌种的粘附模式与单一菌种的结果基本一致:ALD制备的Ti基台上的纳米TiO₂涂层表现出了与ZrO₂表面相当的抗菌性能,这表明其在预防种植体周围炎方面具有潜力。然而,AO 生产的纳米₂ TiO₂涂层的抗细菌和生物膜附着能力有限。
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引用次数: 0
Phytosynthesis, Characterization, Phenolic and Biological Evaluation of Leptadenia pyrotechnica-Based Zn and Fe Nanoparticles Utilizing Two Different Extraction Techniques. 利用两种不同萃取技术对基于烟火藻的锌和铁纳米颗粒进行植物合成、表征、酚类和生物评估
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/IJN.S480716
Rana Ahmed El-Fitiany, Afra AlBlooshi, Abdelouahid Samadi, Mohammad A Khasawneh

Introduction: Phyto-nanotechnology offers a sustainable method for synthesizing biocompatible metal nanoparticles (NPs) with therapeutic potential. The diverse medicinal flora in the UAE, particularly Leptadenia pyrotechnica (LP), provides a vital resource for advancing this research area. This plant is historically valued in the region for its wide medicinal applications due to its abundance of bioactive compounds.

Methods: In this study, eco-friendly, straightforward, and low-temperature hydrothermal synthesis methods were applied to synthesize potentially therapeutic Zn and Fe NPs using LP extracts. The generated NPs were characterized using UV-VIS, FT-IR, SEM, EDX, XRD and DLS. Moreover, they were investigated for their total phenolic and flavonoid contents, along with their antioxidant and skin anticancer effects.

Results: The UV-Vis spectra disclosed absorption band at about 275 nm, and the FT-IR confirmed the successful coating of the NPs with the plants' phytochemicals, thus ensuring the successful bio-fabrication of the proposed NPs. SEM/EDX outcomes suggest a more potent reducing effect of the aqueous extract, while a more effective coating of the alcoholic extract. DLS revealed monodispersed NPs, with average sizes ranging from 43.82 to 207.8 nm. LFeC demonstrated the highest phenolic and flavonoid contents (49.96±4.76 μg of GAE/mg of DW and 43.89±2.89 μg of Qu/mg of DW, respectively) and the greatest potency against skin cancer cell lines (IC50=263.56 µg/mL). However, LZnC exhibited the strongest radical scavenging effect against DPPH and ABTS radicals (IC50=139.45µg/mL and 35.1µg/mL, respectively).

Discussion: The results of this study demonstrated that both extracts of LP are effective in the green synthesis of Fe and Zn nanoparticles for biomedical applications, with alcoholic extracts providing superior coating, capping, and stabilizing properties, leading to lower agglomeration, higher carbon content, total phenolic and flavonoid contents, along with enhanced anticancer and antioxidant effects. This work gives a showcase of sustainable materials that are promising for therapeutic applications.

导言:植物纳米技术为合成具有治疗潜力的生物相容性金属纳米粒子(NPs)提供了一种可持续的方法。阿联酋多样的药用植物群,尤其是烟火菩提(Leptadenia pyrotechnica,LP),为推进这一研究领域提供了重要资源。这种植物因其丰富的生物活性化合物而在该地区具有广泛的药用价值:本研究采用环保、简单和低温水热合成法,利用 LP 提取物合成具有潜在治疗作用的锌和铁 NPs。利用 UV-VIS、FT-IR、SEM、EDX、XRD 和 DLS 对生成的 NPs 进行了表征。此外,还研究了它们的总酚和类黄酮含量,以及它们的抗氧化和皮肤抗癌效果:结果:紫外可见光谱显示了约 275 纳米处的吸收带,傅立叶变换红外光谱证实了 NPs 上成功涂覆了植物的植物化学物质,从而确保了拟议 NPs 的成功生物制造。SEM/EDX 结果表明,水提取物的还原效果更强,而酒精提取物的包覆效果更好。DLS 显示了单分散 NPs,平均尺寸为 43.82 至 207.8 nm。LFeC 的酚类和类黄酮含量最高(分别为 49.96±4.76 μg GAE/mg(干重)和 43.89±2.89 μg Qu/mg(干重)),对皮肤癌细胞株的药效最强(IC50=263.56 µg/mL)。然而,LZnC 对 DPPH 和 ABTS 自由基的清除效果最强(IC50 分别为 139.45µg/mL 和 35.1µg/mL):本研究结果表明,LP 的两种提取物都能有效地绿色合成用于生物医学的铁和锌纳米粒子,其中酒精提取物具有优异的包覆、封盖和稳定特性,可降低团聚,提高碳含量、总酚和类黄酮含量,同时增强抗癌和抗氧化效果。这项工作展示了有望用于治疗的可持续材料。
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引用次数: 0
Unexpected Inhibitory Role of Silica Nanoparticles on Lung Cancer Development by Promoting M1 Polarization of Macrophages. 纳米二氧化硅颗粒通过促进巨噬细胞的 M1 极化对肺癌的发展起到意想不到的抑制作用
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/IJN.S472796
Meng Xiang, Chengzhi Chen, Yuting Chen, Yuhan Zhang, Lei Shi, Yan Chen, Jie Li, Bowen Li, Bin Zeng, H Rosie Xing, Jianyu Wang, Zhen Zou

Introduction: Inhalation exposure to silica nanoparticles (SiNPs) is frequently inevitable in modern times. Although the impact of SiNPs on the ecological niche of the lungs has been extensively explored, the role and mechanism of SiNPs in the microenvironment of lung tumors remain elusive.

Methods: In this investigation, Lewis lung carcinoma (LLC) was implanted into the left lung in situ after 28 days of intratracheal SiNPs injection into the lungs of mice. This study evaluates the effects of SiNPs on the tumor immune microenvironment both in vitro and in vivo. Our findings indicate that SiNPs can suppress lung cancer by modulating the immune microenvironment of tumors.

Results: SiNPs treatment promotes macrophage M1 polarization by activating both NF-κB pathway and glycolytic mechanisms. This phenomenon may be associated with lung inflammation and fluctuation in the pre-metastatic and metastatic microenvironments induced by SiNPs exposure in mice. Additionally, we have shown for the first time that SiNPs have an inhibitory effect on lung carcinogenesis and its progression.

Conclusion: This study uniquely demonstrates that SiNPs suppress lung cancer by promoting M1 polarization of macrophages in the immune microenvironment of lung tumors. Our findings are critical in exploring the interaction between SiNPs and lung cancer.

导言:现代人经常不可避免地吸入二氧化硅纳米粒子(SiNPs)。尽管人们已经广泛探讨了 SiNPs 对肺部生态位的影响,但 SiNPs 在肺部肿瘤微环境中的作用和机制仍然难以捉摸:在本研究中,小鼠肺部气管内注射SiNPs 28天后,将Lewis肺癌(LLC)原位植入左肺。本研究评估了 SiNPs 在体外和体内对肿瘤免疫微环境的影响。我们的研究结果表明,SiNPs 可以通过调节肿瘤的免疫微环境来抑制肺癌:结果:SiNPs 通过激活 NF-κB 通路和糖酵解机制促进巨噬细胞 M1 极化。这一现象可能与小鼠暴露于 SiNPs 所诱发的肺部炎症以及转移前和转移后微环境的波动有关。此外,我们还首次证明了 SiNPs 对肺癌的发生和发展具有抑制作用:本研究独特地证明了 SiNPs 可通过促进肺肿瘤免疫微环境中巨噬细胞的 M1 极化来抑制肺癌。我们的研究结果对于探索 SiNPs 与肺癌之间的相互作用至关重要。
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引用次数: 0
Advancing Photodynamic Therapy with Nano-Conjugated Hypocrellin: Mechanisms and Clinical Applications. 利用纳米结合的 Hypocrellin 推进光动力疗法:机理与临床应用。
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/IJN.S486014
Sheeja S Rajan, Rahul Chandran, Heidi Abrahamse

Hypocrellin-based photodynamic therapy (PDT) is developing as a viable cancer therapeutic option, especially when enhanced by nanoconjugation. This review investigates the methods by which nano-conjugated hypocrellin enhances therapeutic efficacy and precision when targeting cancer cells. These nanoconjugates encapsulate or covalently bind hypocrellin photosensitizers (PSs), allowing them to accumulate preferentially in malignancies. When activated by light, the nanoconjugates produce singlet oxygen and other reactive oxygen species (ROS), resulting in oxidative stress that selectively destroys cancer cells while protecting healthy tissues. We look at how they can be used to treat a variety of cancers. Clinical and preclinical studies show that they have advantages such as increased water solubility, improved tumor penetration, longer circulation times, and tailored delivery, all of which contribute to fewer off-target effects and overall toxicity. Ongoing research focuses on improving these nanoconjugates for better tumor targeting, drug release kinetics, and overcoming biological obstacles. Furthermore, the incorporation of developing technologies such as stimuli-responsive nanocarriers and combination therapies opens exciting opportunities for enhancing hypocrellin-based PDT. In conclusion, the combination of hypocrellin and nanotechnology constitutes a significant approach to cancer treatment, increasing the efficacy and safety of PDT. Future research will seek to create conjugates including hypocrellin, herceptin, and gold nanoparticles to induce apoptosis in human breast cancer cells in vitro, opening possibilities for therapeutic applications.

基于次黄嘌呤的光动力疗法(PDT)正在发展成为一种可行的癌症治疗方法,尤其是在纳米共轭的作用下。本综述研究了纳米共轭次氯酸钠在靶向癌细胞时提高疗效和精确度的方法。这些纳米共轭物封装或共价结合了次氯霉素光敏剂(PSs),使其优先在恶性肿瘤中积聚。当被光激活时,纳米共轭物会产生单线态氧和其他活性氧(ROS),从而产生氧化应激,选择性地破坏癌细胞,同时保护健康组织。我们将探讨如何利用它们治疗各种癌症。临床和临床前研究表明,它们具有增加水溶性、改善肿瘤穿透性、延长循环时间和定制给药等优势,所有这些都有助于减少脱靶效应和总体毒性。目前的研究重点是改进这些纳米共轭物,以提高肿瘤靶向性、药物释放动力学和克服生物障碍。此外,刺激响应型纳米载体和联合疗法等新技术的应用也为增强基于次氯酸钠的光导疗法带来了令人兴奋的机遇。总之,次氯雷林与纳米技术的结合是治疗癌症的重要方法,可提高光动力疗法的疗效和安全性。未来的研究将寻求创建包括次黄嘌呤、赫赛汀和金纳米粒子的共轭物,以诱导体外人类乳腺癌细胞凋亡,为治疗应用提供可能性。
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引用次数: 0
Zeolitic Imidazolate Framework-8 Offers an Anti-Inflammatory and Antifungal Method in the Treatment of Aspergillus Fungal Keratitis in vitro and in vivo. 沸石咪唑酸盐框架-8 在体外和体内治疗曲霉真菌性角膜炎中提供了一种抗炎和抗真菌方法。
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/IJN.S480800
Xueyun Fu, Xue Tian, Jing Lin, Qian Wang, Lingwen Gu, Ziyi Wang, Menghui Chi, Bing Yu, Zhuhui Feng, Wenyao Liu, Lina Zhang, Cui Li, Guiqiu Zhao

Background: Fungal keratitis is a serious blinding eye disease. Traditional drugs used to treat fungal keratitis commonly have the disadvantages of low bioavailability, poor dispersion, and limited permeability.

Purpose: To develop a new method for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability.

Methods: Zeolitic Imidazolate Framework-8 (ZIF-8) was formed by zinc ions and 2-methylimidazole linked by coordination bonds and characterized by Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Zeta potential. The safety of ZIF-8 on HCECs and RAW 264.7 cells was detected by Cell Counting Kit-8 (CCK-8). Safety evaluation of ZIF-8 on mice corneal epithelium was conducted using the Draize corneal toxicity test. The effects of ZIF-8 on fungal growth, biofilm formation, and hyphae structure were detected by Minimal inhibit concentration (MIC), crystal violet staining, Propidium Iodide (PI) testing, and calcofluor white staining. The anti-inflammatory effects of ZIF-8 on RAW 246.7 cells were evaluated by Quantitative Real-Time PCR Experiments (qPCR) and Enzyme-linked immunosorbent assay (ELISA). Clinical score, Colony-Forming Units (CFU), Hematoxylin-eosin (HE) staining, and immunofluorescence were conducted to verify the therapeutic effect of ZIF-8 on C57BL/6 female mice with fungal keratitis.

Results: In vitro, ZIF-8 showed outstanding antifungal effects, including inhibiting the growth of Aspergillus fumigatus over 90% at 64 μg/mL, restraining the formation of biofilm, and destroying cell membranes. In vivo, treatment with ZIF-8 reduced corneal fungal load and mitigated neutrophil infiltration in fungal keratitis, which effectively reduced the severity of keratitis in mice and alleviated the infiltration of inflammatory factors in the mouse cornea. In addition, ZIF-8 reduces the inflammatory response by downregulating the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β after Aspergillus fumigatus infection in vivo and in vitro.

Conclusion: ZIF-8 has a significant anti-inflammatory and antifungal effect, which provides a new solution for the treatment of fungal keratitis.

背景:真菌性角膜炎是一种严重的致盲性眼病:真菌性角膜炎是一种严重的致盲性眼病。用于治疗真菌性角膜炎的传统药物普遍存在生物利用度低、分散性差、渗透性有限等缺点。目的:开发一种可改善生物利用度、分散性和渗透性的治疗真菌性角膜炎的新方法:方法:锌离子和 2-甲基咪唑通过配位键连接形成沸石咪唑酸框架-8(ZIF-8),并通过扫描电子显微镜(SEM)、X 射线衍射(XRD)和 Zeta 电位对其进行表征。细胞计数试剂盒-8(CCK-8)检测了 ZIF-8 对 HCECs 和 RAW 264.7 细胞的安全性。采用 Draize 角膜毒性试验评估了 ZIF-8 对小鼠角膜上皮细胞的安全性。通过最小抑菌浓度(MIC)、水晶紫染色、碘化丙啶(PI)检测和钙氟白染色检测 ZIF-8 对真菌生长、生物膜形成和菌丝结构的影响。实时定量 PCR 实验(qPCR)和酶联免疫吸附试验(ELISA)评估了 ZIF-8 对 RAW 246.7 细胞的抗炎作用。临床评分、菌落形成单位(CFU)、苏木精-伊红(HE)染色和免疫荧光验证了 ZIF-8 对 C57BL/6 雌性真菌性角膜炎小鼠的治疗效果:结果:在体外,ZIF-8 表现出突出的抗真菌效果,包括在 64 μg/mL 的浓度下抑制烟曲霉生长超过 90%,抑制生物膜的形成,破坏细胞膜。在体内,用 ZIF-8 治疗可降低真菌性角膜炎的角膜真菌负荷,减轻中性粒细胞浸润,从而有效减轻小鼠角膜炎的严重程度,缓解小鼠角膜炎症因子的浸润。此外,ZIF-8 还能通过下调曲霉菌体内和体外感染后促炎细胞因子 TNF-α、IL-6 和 IL-1β 的表达来减轻炎症反应:ZIF-8具有明显的抗炎和抗真菌作用,为治疗真菌性角膜炎提供了一种新的解决方案。
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引用次数: 0
Iron-Based Nanoplatforms Achieve Hepatocellular Carcinoma Regression Through a Cascade of Effects. 铁基纳米平台通过一系列效应实现肝细胞癌的消退
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/IJN.S479425
Kunzhao Huang, Xiaoyuan Yi, Huaying Xie, Jianzhang Luo, Qingyu Zeng, Feifei He, Liyan Wang
<p><strong>Purpose: </strong>Ferroptosis is a regulated form of cell death characterized by iron-dependent accumulation of associated lipid peroxides (LPO), which can induce cell death when a certain level is reached. However, the extremely complex tumor microenvironment (TME) has the characteristics of antioxidant, even if it induces ferroptosis of tumor cells, its killing effect on tumor cells is still very limited. To solve this problem, we constructed a novel nanomaterials (GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM). We evaluated the anticancer effect of this nanomaterial in inhibiting tumor growth through comprehensive in vitro and in vivo experiments.</p><p><strong>Methods: </strong>We successfully synthesized GOx/EC@Fe<sub>3</sub>O<sub>4</sub> by one-pan synthesis method, then coated the Hepatocellular carcinoma cell membrane on its surface by co-extrusion technology, and finally synthesized the GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM nanoplatforms. We characterized the compounds in terms of morphology, particle size, and Zeta potential. In addition, we also studied the anti-tumor effect of GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM nanoplatforms from the following aspects, including the performance test of the nanoplatform, the intracellular effect of the nanoplatform, the anti-tumor effect in vitro, the intracellular ROS analysis, the intracellular effect of EC, and the anti-tumor effect in vivo.</p><p><strong>Results: </strong>The iron-based carriers in GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM nanoplatforms are released and produce ferrous ions (Fe<sup>2+</sup>) in an acidic environment. Due to the limitation of the endogenous level of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), we introduced GOx into the TME or tumor cells. Under the catalysis of GOx, glucose reacted rapidly to produce a large amount of H<sub>2</sub>O<sub>2</sub>, which then combined with Fe<sup>2+</sup> to produce a large number of Hydroxyl radical (·OH). Its toxicity leads to dysfunction of cell membrane and organelles, and then causes cell damage. EC inhibits Nuclear factor erythroid 2-related factor 2 (Nrf2) in cancer cells, which effectively down-regulates downstream gene products, including NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HMOX1). A series of chain reactions reduce the escape effect of oxidative stress (OS) and effectively maintain a high level of intracellular oxidation. Furthermore, it induces sustained and intense ferroptosis in tumor cells. Finally, the use of cancer cell membrane modified nanoplatforms due to the homology of membrane protein components improves the tumor cell targeting of the nanoplatforms, showing significant tumor cell inhibition and killing effect in vivo.</p><p><strong>Conclusion: </strong>The results showed that the GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM nanoplatforms successfully induced significant ferroptosis of Hepatocellular carcinoma cells through a cascade effect, and finally effectively promoted cancer cel
目的铁氧化是一种调节性细胞死亡形式,其特征是相关脂质过氧化物(LPO)的铁依赖性积累,当达到一定水平时可诱导细胞死亡。然而,极其复杂的肿瘤微环境(TME)具有抗氧化的特性,即使能诱导肿瘤细胞的铁跃迁,其对肿瘤细胞的杀伤作用仍然非常有限。为了解决这个问题,我们构建了一种新型纳米材料(GOx/EC@Fe3O4@CCM)。我们通过体外和体内综合实验评估了这种纳米材料在抑制肿瘤生长方面的抗癌效果:方法:我们采用单泛合成法成功合成了GOx/EC@Fe3O4,然后通过共挤技术在其表面包覆了肝癌细胞膜,最后合成了GOx/EC@Fe3O4@CCM纳米平台。我们对化合物的形态、粒度和 Zeta 电位进行了表征。此外,我们还从纳米平台的性能测试、纳米平台的细胞内效应、体外抗肿瘤效应、细胞内ROS分析、EC的细胞内效应和体内抗肿瘤效应等方面研究了GOx/EC@Fe3O4@CCM纳米平台的抗肿瘤效应:结果:GOx/EC@Fe3O4@CCM纳米平台中的铁基载体在酸性环境中释放并产生亚铁离子(Fe2+)。由于内源性过氧化氢(H2O2)水平的限制,我们将 GOx 引入 TME 或肿瘤细胞中。在 GOx 的催化作用下,葡萄糖迅速反应产生大量 H2O2,然后与 Fe2+ 结合产生大量羟自由基(-OH)。其毒性导致细胞膜和细胞器功能失调,进而造成细胞损伤。EC 可抑制癌细胞中的核因子红细胞 2 相关因子 2(Nrf2),从而有效下调下游基因产物,包括 NAD(P)H 醌氧化还原酶 1(NQO1)和血红素加氧酶 1(HMOX1)。一系列连锁反应降低了氧化应激(OS)的逃逸效应,有效维持了细胞内的高水平氧化。此外,它还能诱导肿瘤细胞发生持续而强烈的铁变态反应。最后,由于膜蛋白成分的同源性,使用癌细胞膜修饰的纳米平台提高了纳米平台的肿瘤细胞靶向性,在体内显示出显著的肿瘤细胞抑制和杀伤效果:结果表明,GOx/EC@Fe3O4@CCM纳米平台通过级联效应成功诱导了肝癌细胞的显著铁变态反应,并最终有效促进了癌细胞的消退。
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引用次数: 0
TME-Activated MnO2/Pt Nanoplatform of Hydroxyl Radical and Oxygen Generation to Synergistically Promote Radiotherapy and MR Imaging of Glioblastoma. TME激活的MnO2/Pt纳米平台产生羟基自由基和氧气,协同促进胶质母细胞瘤的放射治疗和磁共振成像。
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/IJN.S474098
Lijuan Chen, Mingbo Liu, Yunjuan Wang, Wei Wei, Yaqiong Li, Yan Bai, Xuan Yu, Lei Jiao, Meiyun Wang

Purpose: Radiotherapy (RT) is currently recognized as an important treatment for glioblastoma (GBM), however, it is associated with several challenges. One of these challenges is the radioresistance caused by hypoxia, whereas the other is the low conversion efficiency of the strongly oxidized hydroxyl radical (•OH), which is produced by the decomposition of water due to high-energy X-ray radiation. These factors significantly limit the clinical effectiveness of radiotherapy.

Results: To address these limitations, we developed a highly stable and efficient nanoplatform (MnO2/Pt@BSA). Compared to MnO2@BSA, this platform demonstrates high stability, a high yield of oxygen (O2), enhanced production of •OH, and reduced clearance of •OH. The system exhibited increased O2 production in vitro and significantly improved oxygen production efficiency within 100 s at the Pt loading of 38.7%. Furthermore, compared with MnO2, the expression rate of hypoxia-inducible factor (HIF-1α) in glioma cells treated with MnO2/Pt decreased by half. Additionally, the system promotes •OH generation and consumes glutathione (GSH), thereby inhibiting the clearance of •OH and enhancing its therapeutic effect. Moreover, the degradation of the nanoplatform produces Mn2+, which serves as a magnetic resonance imaging (MRI) contrast agent with a T1-weighted enhancement effect at the tumor site. The nanoplatform exhibited excellent biocompatibility and performed multiple functions related to radiotherapy, with simpler components. In U87 tumor bearing mice model, we utilized MnO2/Pt nanocatalysis to enhance the therapeutic effect of radiotherapy on GBM.

Conclusion: This approach represents a novel and effective strategy for enhancing radiotherapy in gliomas, thereby advancing the field of catalytic radiotherapy and glioma treatment.

目的:放射治疗(RT)是目前公认的治疗胶质母细胞瘤(GBM)的重要方法,但它也面临着一些挑战。其中一个挑战是缺氧引起的放射抵抗,另一个挑战是强氧化羟基自由基(-OH)的转化效率低,这种自由基是由高能 X 射线辐射分解水产生的。这些因素极大地限制了放射治疗的临床效果:针对这些限制因素,我们开发了一种高度稳定、高效的纳米平台(MnO2/Pt@BSA)。与 MnO2@BSA 相比,该平台具有高稳定性、高氧气(O2)产量、更高的 -OH 产量以及更低的 -OH 清除率。该系统在体外表现出更高的氧气产量,在铂载量为 38.7% 时,氧气产量效率在 100 秒内显著提高。此外,与 MnO2 相比,用 MnO2/Pt 处理的胶质瘤细胞中缺氧诱导因子(HIF-1α)的表达率降低了一半。此外,该系统还能促进 -OH 的生成并消耗谷胱甘肽(GSH),从而抑制 -OH 的清除并增强其治疗效果。此外,纳米平台降解产生的 Mn2+ 可作为磁共振成像(MRI)造影剂,在肿瘤部位产生 T1 加权增强效应。该纳米平台具有良好的生物相容性,能以更简单的成分实现与放疗相关的多种功能。在 U87 肿瘤小鼠模型中,我们利用 MnO2/Pt 纳米催化增强了放疗对 GBM 的治疗效果:结论:这种方法是增强胶质瘤放疗的一种新颖而有效的策略,从而推动了催化放疗和胶质瘤治疗领域的发展。
{"title":"TME-Activated MnO<sub>2</sub>/Pt Nanoplatform of Hydroxyl Radical and Oxygen Generation to Synergistically Promote Radiotherapy and MR Imaging of Glioblastoma.","authors":"Lijuan Chen, Mingbo Liu, Yunjuan Wang, Wei Wei, Yaqiong Li, Yan Bai, Xuan Yu, Lei Jiao, Meiyun Wang","doi":"10.2147/IJN.S474098","DOIUrl":"10.2147/IJN.S474098","url":null,"abstract":"<p><strong>Purpose: </strong>Radiotherapy (RT) is currently recognized as an important treatment for glioblastoma (GBM), however, it is associated with several challenges. One of these challenges is the radioresistance caused by hypoxia, whereas the other is the low conversion efficiency of the strongly oxidized hydroxyl radical (•OH), which is produced by the decomposition of water due to high-energy X-ray radiation. These factors significantly limit the clinical effectiveness of radiotherapy.</p><p><strong>Results: </strong>To address these limitations, we developed a highly stable and efficient nanoplatform (MnO<sub>2</sub>/Pt@BSA). Compared to MnO<sub>2</sub>@BSA, this platform demonstrates high stability, a high yield of oxygen (O<sub>2</sub>), enhanced production of •OH, and reduced clearance of •OH. The system exhibited increased O<sub>2</sub> production in vitro and significantly improved oxygen production efficiency within 100 s at the Pt loading of 38.7%. Furthermore, compared with MnO<sub>2</sub>, the expression rate of hypoxia-inducible factor (HIF-1α) in glioma cells treated with MnO<sub>2</sub>/Pt decreased by half. Additionally, the system promotes •OH generation and consumes glutathione (GSH), thereby inhibiting the clearance of •OH and enhancing its therapeutic effect. Moreover, the degradation of the nanoplatform produces Mn<sup>2+</sup>, which serves as a magnetic resonance imaging (MRI) contrast agent with a T<sub>1</sub>-weighted enhancement effect at the tumor site. The nanoplatform exhibited excellent biocompatibility and performed multiple functions related to radiotherapy, with simpler components. In U87 tumor bearing mice model, we utilized MnO<sub>2</sub>/Pt nanocatalysis to enhance the therapeutic effect of radiotherapy on GBM.</p><p><strong>Conclusion: </strong>This approach represents a novel and effective strategy for enhancing radiotherapy in gliomas, thereby advancing the field of catalytic radiotherapy and glioma treatment.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Breast Cancer Chemoprevention from Nano Zingiber officinale Roscoe. 从纳米细辛中预防乳腺癌。
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/IJN.S474611
Andika Pramudya Wardana, Alfinda Novi Kristanti, Nanik Siti Aminah, Mochamad Zakki Fahmi, Muggundha Raoov, Indriani

Background: After cardiovascular disease, cancer is one of the leading causes of death due to uncontrolled cell growth. Breast cancer is among the most prevalent types of cancer. Zingiber officinale Roscoe. rich in phenolic compounds, which can stimulate and function as endogenous antioxidants.

Purpose: Investigation of the in vivo chemopreventive has the potential of nano Z. officinale Roscoe (Zo-NPs) in breast cancer.

Study design: Using female Mus musculus Balb/c induced with benzo[α]pyrene, the chemopreventive action of Z. officinale Roscoe. nanoencapsulated using κ-carrageenan was assessed.

Results: Z. officinale Roscoe Extract. contains 58 compounds, with the main component being [6]-gingerol with [6]-gingerol content being 697.65 ± 8.52 mg/g extract. Nanoencapsulation of Z. officinale Roscoe. has been successfully prepared with a particle size of 483.30 ± 11.23 nm. Zo-NPs are generally resistant to pH, temperature, and salt content variations. Compared to group C1, which underwent ductular dilatation, the administration of Zo-NPs (group T2) to female Mus musculus Balb/c, induced by benzo[α]pyrene, revealed no histological alterations in breast tissue. Moreover, administering Zo-NPs can raise blood serum levels of CAT, GSH, and SOD. In addition, it showed a greater ability to lower TNF-α levels than the T1 group, which received Z. officinale Roscoe extract. (Zo).

背景:癌症是继心血管疾病之后,因细胞生长失控而导致死亡的主要原因之一。乳腺癌是最常见的癌症类型之一。目的:研究纳米 Z. officinale Roscoe(Zo-NPs)对乳腺癌的体内化学预防潜力:研究设计:使用苯并[α]芘诱导雌性麝香鹿Balb/c,评估了使用κ-卡拉胶封装的纳米欧当归(Z. officinale Roscoe)的化学预防作用:含有 58 种化合物,主要成分为[6]-姜酚,[6]-姜酚含量为 697.65 ± 8.52 mg/g。已成功制备出 Z. officinale Roscoe.纳米胶囊,粒径为 483.30 ± 11.23 nm。Zo-NPs 一般能抵抗 pH 值、温度和盐含量的变化。在苯并[α]芘的诱导下,雌性巴尔/克麝香猫服用 Zo-NPs (T2 组)后,乳腺组织没有发生组织学改变,而 C1 组乳腺导管扩张。此外,服用 Zo-NPs 还能提高血清中 CAT、GSH 和 SOD 的水平。此外,与接受 Z. officinale Roscoe 提取物的 T1 组相比,它降低 TNF-α 水平的能力更强。(Zo)。
{"title":"Breast Cancer Chemoprevention from Nano <i>Zingiber officinale</i> Roscoe.","authors":"Andika Pramudya Wardana, Alfinda Novi Kristanti, Nanik Siti Aminah, Mochamad Zakki Fahmi, Muggundha Raoov, Indriani","doi":"10.2147/IJN.S474611","DOIUrl":"10.2147/IJN.S474611","url":null,"abstract":"<p><strong>Background: </strong>After cardiovascular disease, cancer is one of the leading causes of death due to uncontrolled cell growth. Breast cancer is among the most prevalent types of cancer. <i>Zingiber officinale</i> Roscoe. rich in phenolic compounds, which can stimulate and function as endogenous antioxidants.</p><p><strong>Purpose: </strong>Investigation of the in vivo chemopreventive has the potential of nano <i>Z. officinale</i> Roscoe (Zo-NPs) in breast cancer.</p><p><strong>Study design: </strong>Using female <i>Mus musculus</i> Balb/c induced with benzo[α]pyrene, the chemopreventive action of <i>Z. officinale</i> Roscoe. nanoencapsulated using κ-carrageenan was assessed.</p><p><strong>Results: </strong><i>Z. officinale</i> Roscoe Extract. contains 58 compounds, with the main component being [6]-gingerol with [6]-gingerol content being 697.65 ± 8.52 mg/g extract. Nanoencapsulation of <i>Z. officinale</i> Roscoe. has been successfully prepared with a particle size of 483.30 ± 11.23 nm. Zo-NPs are generally resistant to pH, temperature, and salt content variations. Compared to group C<sub>1</sub>, which underwent ductular dilatation, the administration of Zo-NPs (group T<sub>2</sub>) to female <i>Mus musculus</i> Balb/c, induced by benzo[α]pyrene, revealed no histological alterations in breast tissue. Moreover, administering Zo-NPs can raise blood serum levels of CAT, GSH, and SOD. In addition, it showed a greater ability to lower TNF-α levels than the T<sub>1</sub> group, which received <i>Z. officinale</i> Roscoe extract. (Zo).</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization and Performance Evaluation of Magnesium Chloride-Enriched Polyurethane Nanofiber Patches for Wound Dressings. 用于伤口敷料的富氯化镁聚氨酯纳米纤维贴片的特性和性能评估。
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/IJN.S460921
Mohan Prasath Mani, Hemanth Ponnambalath Mohanadas, Ahmad Athif Mohd Faudzi, Ahmad Fauzi Ismail, Nick Tucker, Shahrol Mohamaddan, Manikandan Ayyar, Tamilselvam Palanisamy, Rajasekar Rathanasamy, Saravana Kumar Jaganathan

Purpose: Wound patches are essential for wound healing, yet developing patches with enhanced mechanical and biological properties remains challenging. This study aimed to enhance the mechanical and biological properties of polyurethane (PU) by incorporating magnesium chloride (MgCl2) into the patch.

Methodology: The composite patch was fabricated using the electrospinning technique, producing nanofibers from a mixture of PU and MgCl2 solutions. The electrospun PU/MgCl2 was then evaluated for various physico-chemical characteristics and biological properties to determine its suitability for wound healing applications.

Results: Tensile strength testing showed that the mechanical properties of the composite patch (10.98 ± 0.18) were significantly improved compared to pristine PU (6.66 ± 0.44). Field scanning electron microscopy (FESEM) revealed that the electrospun nanofiber patch had a smooth, randomly oriented non-woven structure (PU - 830 ± 145 nm and PU/MgCl2 - 508 ± 151 nm). Fourier infrared spectroscopy (FTIR) confirmed magnesium chloride's presence in the polyurethane matrix via strong hydrogen bond formation. Blood compatibility studies using coagulation assays, including activated partial thromboplastin time (APTT), prothrombin time (PT), and hemolysis assays, demonstrated improved blood compatibility of the composite patch (APTT - 174 ± 0.5 s, PT - 91 ± 0.8s, and Hemolytic percentage - 1.78%) compared to pristine PU (APTT - 152 ± 1.2s, PT - 73 ± 1.7s, and Hemolytic percentage - 2.55%). Antimicrobial testing showed an enhanced zone of inhibition (Staphylococcus aureus - 21.5 ± 0.5 mm and Escherichia coli - 27.5 ± 2.5 mm) compared to the control, while cell viability assays confirmed the non-cytotoxic nature of the developed patches on fibroblast cells.

Conclusion: The study concludes that adding MgCl2 to PU significantly improves the mechanical, biological, and biocompatibility properties of the patch. This composite patch shows potential for future wound healing applications, with further studies needed to validate its efficacy in-vivo.

目的:伤口贴片对伤口愈合至关重要,但开发具有更强机械和生物特性的贴片仍具有挑战性。本研究旨在通过在补片中加入氯化镁(MgCl2)来增强聚氨酯(PU)的机械和生物特性:方法:使用电纺丝技术制造复合贴片,从聚氨酯和氯化镁溶液的混合物中产生纳米纤维。然后评估了电纺聚氨酯/氯化镁的各种物理化学特性和生物特性,以确定其是否适合伤口愈合应用:结果:拉伸强度测试表明,与原始聚氨酯(6.66 ± 0.44)相比,复合贴片的机械性能(10.98 ± 0.18)明显提高。现场扫描电子显微镜(FESEM)显示,电纺纳米纤维贴片具有平滑、随机取向的无纺结构(聚氨酯 - 830 ± 145 nm,聚氨酯/氯化镁 - 508 ± 151 nm)。傅立叶红外光谱(FTIR)证实,氯化镁通过强氢键形成存在于聚氨酯基质中。使用凝血测定法(包括活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)和溶血测定法)进行的血液相容性研究表明,与原始聚氨酯(APTT - 152 ± 1.2s,PT - 73 ± 1.7s,溶血率 - 2.55%)相比,复合贴片的血液相容性更好(APTT - 174 ± 0.5s,PT - 91 ± 0.8s,溶血率 - 1.78%)。抗菌测试表明,与对照组相比,金黄色葡萄球菌抑制区(21.5 ± 0.5 mm)和大肠杆菌抑制区(27.5 ± 2.5 mm)有所扩大:研究得出结论:在聚氨酯中添加氯化镁能显著改善补片的机械、生物和生物相容性。这种复合贴片显示出未来伤口愈合应用的潜力,但还需要进一步的研究来验证其体内疗效。
{"title":"Characterization and Performance Evaluation of Magnesium Chloride-Enriched Polyurethane Nanofiber Patches for Wound Dressings.","authors":"Mohan Prasath Mani, Hemanth Ponnambalath Mohanadas, Ahmad Athif Mohd Faudzi, Ahmad Fauzi Ismail, Nick Tucker, Shahrol Mohamaddan, Manikandan Ayyar, Tamilselvam Palanisamy, Rajasekar Rathanasamy, Saravana Kumar Jaganathan","doi":"10.2147/IJN.S460921","DOIUrl":"10.2147/IJN.S460921","url":null,"abstract":"<p><strong>Purpose: </strong>Wound patches are essential for wound healing, yet developing patches with enhanced mechanical and biological properties remains challenging. This study aimed to enhance the mechanical and biological properties of polyurethane (PU) by incorporating magnesium chloride (MgCl<sub>2</sub>) into the patch.</p><p><strong>Methodology: </strong>The composite patch was fabricated using the electrospinning technique, producing nanofibers from a mixture of PU and MgCl<sub>2</sub> solutions. The electrospun PU/MgCl<sub>2</sub> was then evaluated for various physico-chemical characteristics and biological properties to determine its suitability for wound healing applications.</p><p><strong>Results: </strong>Tensile strength testing showed that the mechanical properties of the composite patch (10.98 ± 0.18) were significantly improved compared to pristine PU (6.66 ± 0.44). Field scanning electron microscopy (FESEM) revealed that the electrospun nanofiber patch had a smooth, randomly oriented non-woven structure (PU - 830 ± 145 nm and PU/MgCl<sub>2</sub> - 508 ± 151 nm). Fourier infrared spectroscopy (FTIR) confirmed magnesium chloride's presence in the polyurethane matrix via strong hydrogen bond formation. Blood compatibility studies using coagulation assays, including activated partial thromboplastin time (APTT), prothrombin time (PT), and hemolysis assays, demonstrated improved blood compatibility of the composite patch (APTT - 174 ± 0.5 s, PT - 91 ± 0.8s, and Hemolytic percentage - 1.78%) compared to pristine PU (APTT - 152 ± 1.2s, PT - 73 ± 1.7s, and Hemolytic percentage - 2.55%). Antimicrobial testing showed an enhanced zone of inhibition (Staphylococcus aureus - 21.5 ± 0.5 mm and Escherichia coli - 27.5 ± 2.5 mm) compared to the control, while cell viability assays confirmed the non-cytotoxic nature of the developed patches on fibroblast cells.</p><p><strong>Conclusion: </strong>The study concludes that adding MgCl<sub>2</sub> to PU significantly improves the mechanical, biological, and biocompatibility properties of the patch. This composite patch shows potential for future wound healing applications, with further studies needed to validate its efficacy in-vivo.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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International Journal of Nanomedicine
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