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Formulation and evaluation of PVA-based composite hydrogels: physicochemical, leachables, and in vitro immunogenicity studies. pva基复合水凝胶的配方和评价:理化、可浸出性和体外免疫原性研究。
Pub Date : 2025-01-15 DOI: 10.1039/d4tb02181a
Achmad Himawan, Anna Korelidou, Ana M Pérez-Moreno, Juan L Paris, Juan Dominguez-Robles, Lalitkumar K Vora, Andi Dian Permana, Eneko Larrañeta, Robert Graham, Christopher J Scott, Ryan F Donnelly

This study explores the formulation and characterization of poly(vinyl alcohol) (PVA)-based composite hydrogels synthesized through solid-state crosslinking. Comprehensive assessments were conducted on their physicochemical properties, leachables, and immunogenicity. Swelling experiments demonstrated that the incorporation of poly(vinylpyrrolidone) (PVP) enhanced water retention, while chitosan had a minimal effect on swelling behavior. Qualitative analysis of leachables identified water-soluble components, including dehydrated PVA and PVP. Fourier-transform infrared (FTIR) spectroscopy confirmed the formation of ester bonds and indicated increased hydrogen bonding post-crosslinking. Thermal stability was validated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), with decomposition observed at 320-330 °C. X-ray diffraction (XRD) analysis revealed enhanced crystallinity following crosslinking. Solid-state nuclear magnetic resonance (NMR) further confirmed chemical changes consistent with the results from other characterization techniques. In vitro assays using DC2.4 mouse dendritic cells showed that hydrogel extracts inhibited cell proliferation without causing cytotoxicity or triggering significant immune responses. These findings highlight the hydrogels' biocompatibility and stability, supporting their potential for biomedical applications.

本研究探讨了固态交联法制备聚乙烯醇(PVA)基复合水凝胶的配方及表征。对其理化性质、可浸性和免疫原性进行了综合评价。膨胀实验表明,聚乙烯吡咯烷酮(PVP)的加入增强了水潴留,而壳聚糖对膨胀行为的影响很小。对浸出液进行定性分析,确定了水溶性成分,包括脱水PVA和PVP。傅里叶变换红外光谱(FTIR)证实了酯键的形成,并表明交联后氢键增加。通过差示扫描量热法(DSC)和热重分析(TGA)验证了热稳定性,在320-330°C时观察到分解。x射线衍射(XRD)分析显示交联后结晶度增强。固体核磁共振(NMR)进一步证实了化学变化,与其他表征技术的结果一致。用DC2.4小鼠树突状细胞进行的体外实验表明,水凝胶提取物抑制细胞增殖,但不会引起细胞毒性或引发显著的免疫反应。这些发现突出了水凝胶的生物相容性和稳定性,支持了它们在生物医学应用方面的潜力。
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引用次数: 0
Effect of surface-engineered AuNPs on gene expression, bacterial interaction, protein denaturation, and toxicology assay: an in vitro and in vivo model. 表面工程AuNPs对基因表达、细菌相互作用、蛋白质变性和毒理学分析的影响:体外和体内模型。
Pub Date : 2025-01-15 DOI: 10.1039/d4tb01731e
A Sowndarya, T Daniel Thangadurai, Nebu George Thomas, Renjith Sreedharan, Sukumaran Anil, N Manjubaashini, T G Satheesh Babu, S Megha Kumar

We investigated the in vitro and in vivo uses of pamoic acid functionalized gold nanoparticles (PA@AuNPs), with a focus on determining their safety and potential toxicity in living beings. To test this theory, the bacterial interaction of PA@AuNPs was studied using Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa cultures, as well as the inhibition of the bovine serum albumin (BSA) protein. The real-time polymerase chain reaction (RT-PCR) is used to measure the expression of target genes. PA@AuNPs caused dose-dependent cell death in MDA-MB-231, a triple-negative breast cancer (BC) cell line, with an LC50 of -42.23 μL mL-1. It also caused apoptosis in BC cells. The results indicated that in the early weeks, inflammatory cells (mostly neutrophils and macrophages) penetrated the connective tissue, but in the latter weeks, a substantial number of fibroblasts and fibrocytes were identified. Changes in vascular channels, extravasated red blood cells (RBCs), and necrosis are all indicators of growing tissue pathology. These data could point to a dynamic process including an anti-inflammatory response followed by tissue remodeling or repair. These findings show that PA@AuNPs were not hazardous to the tested Sprague Dawley rats, are highly biocompatible, and can be used in a variety of biological applications.

我们研究了帕莫酸功能化金纳米粒子(PA@AuNPs)的体外和体内用途,重点是确定其在生物体内的安全性和潜在毒性。为了验证这一理论,我们使用大肠杆菌、金黄色葡萄球菌和铜绿假单胞菌培养物研究了 PA@AuNPs 与细菌的相互作用,以及对牛血清白蛋白(BSA)蛋白的抑制作用。实时聚合酶链反应(RT-PCR)用于测量目标基因的表达。PA@AuNPs 在三阴性乳腺癌(BC)细胞系 MDA-MB-231 中引起剂量依赖性细胞死亡,半数致死浓度为 -42.23 μL mL-1。它还能导致 BC 细胞凋亡。结果表明,在早期几周,炎症细胞(主要是中性粒细胞和巨噬细胞)穿透了结缔组织,但在后期几周,发现了大量的成纤维细胞和纤维细胞。血管通道的变化、外渗的红细胞(RBC)和坏死都是组织病变不断发展的指标。这些数据表明了一个动态过程,包括抗炎反应和组织重塑或修复。这些研究结果表明,PA@AuNPs 对接受测试的 Sprague Dawley 大鼠无害,具有很高的生物相容性,可用于各种生物应用。
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引用次数: 0
Towards cell-adhesive, 4D printable PCL networks through dynamic covalent chemistry. 通过动态共价化学,向细胞粘合剂,4D打印PCL网络。
Pub Date : 2025-01-15 DOI: 10.1039/d4tb02423k
Sagnik Ghosh, Sathiyaraj Subramaniyan, Anadi Bisht, Bhanu Nandan, Ritu Kulshreshtha, Minna Hakkarainen, Rajiv K Srivastava

In recent years, the development of biodegradable, cell-adhesive polymeric implants and minimally invasive surgery has significantly advanced healthcare. These materials exhibit multifunctional properties like self-healing, shape-memory, and cell adhesion, which can be achieved through novel chemical approaches. Engineering of such materials and their scalability using a classical polymer network without complex chemical synthesis and modification has been a great challenge, which potentially can be resolved using biobased dynamic covalent chemistry (DCC). Here, we report a scalable, self-healable, biodegradable, and cell-adhesive poly(ε-caprolactone) (PCL)-based vitrimer scaffold, using imine exchange, free from the limitations of melting transitions and supramolecular interactions in 4D-printed PCL. PCL's typical hydrophobicity hinders cell adhesion; however, our design, based on photopolymerization of PCL-dimethacrylate and methacrylate-terminated vanillin-based imine, achieves a water contact angle of 64°. The polymer network, fabricated in varying proportions, exhibited a co-continuous phase morphology, achieving optimal shape fixity (91 ± 1.7%) and shape recovery (92.5 ± 0.1%) at physiological temperature (37 °C). Additionally, the scaffold promoted cell adhesion and proliferation and reduced oxidative stress at the defect site. This multifunctional material shows the potential of DCC-based research in developing smart biomedical devices with complex geometries, paving the way for novel applications in regenerative medicine and implant design.

近年来,生物可降解、细胞黏附的聚合物植入物和微创手术的发展显著地促进了医疗保健。这些材料具有自我修复、形状记忆和细胞粘附等多功能特性,可以通过新的化学方法实现。这类材料的工程设计及其可扩展性使用经典的聚合物网络,而不需要复杂的化学合成和修饰,这是一个巨大的挑战,有可能通过生物基动态共价化学(DCC)来解决。在这里,我们报告了一种可扩展的、可自我修复的、可生物降解的、基于聚(ε-己内酯)(PCL)的细胞粘附性聚合物支架,利用亚胺交换,不受4d打印PCL中熔融转变和超分子相互作用的限制。PCL的典型疏水性阻碍了细胞的粘附;然而,我们的设计,基于pcl -二甲基丙烯酸酯和甲基丙烯酸酯端部香草素基亚胺的光聚合,实现了64°的水接触角。以不同比例制备的聚合物网络具有共连续相形态,在生理温度(37℃)下具有最佳的形状固定点(91±1.7%)和形状恢复(92.5±0.1%)。此外,支架促进细胞粘附和增殖,减少缺陷部位的氧化应激。这种多功能材料显示了基于dcc的研究在开发具有复杂几何形状的智能生物医学设备方面的潜力,为再生医学和植入物设计的新应用铺平了道路。
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引用次数: 0
Tyrosine-modified tilapia skin antioxidant peptides and their hydroxyl radical quenching activities. 酪氨酸修饰罗非鱼皮抗氧化肽及其羟自由基淬灭活性。
Pub Date : 2025-01-15 DOI: 10.1039/d4tb02200a
Yunyao Wang, Ruiqing Jiu, Zongda Li, Qiuying Wang, Xiangmin Lei, Jianan Chen, Haochi Liu, Jifeng Liu

In an antioxidant peptide study, the number and position of active amino acid sites, as well as the peptides' conformation, are found to be crucial for scavenging hydroxyl radicals (˙OH). Herein, ˙the OH scavenging activity of tilapia pentapeptide (P1, YGDQY) and its analogs including P2 (YYYGDQY), P3 (YYGDQYY) and P4 (YYGPDQYY) was investigated. The results showed that the tyrosine's amount, location and the peptides' conformation played important roles in determining peptides' scavenging activity (34.1 ± 0.8%, 45.1 ± 0.9%, 58.6 ± 1.3% and 48.4 ± 0.96% for P1, P2, P3, and P4, respectively). Density functional theory simulation showed that only the tyrosine sites located within the effective diffusion distance of ˙OH could scavenge the radical. The peptides did not cause cytotoxicity in Caco-2 cells. And the peptide-treated group could increase the activities of glutathione peroxidase (GSH-PX), catalase (CAT) and superoxide dismutase (SOD), and reduced malondialdehyde (MDA) levels. This work may contribute to designing more active antioxidant peptides based on natural peptides' analogs.

在一项抗氧化肽的研究中,活性氨基酸位点的数量和位置以及肽的构象,被发现对清除羟基自由基(˙OH)至关重要。本文研究了罗非鱼五肽(P1, YGDQY)及其类似物P2 (YYYGDQY)、P3 (YYGDQYY)和P4 (YYGPDQYY)的OH清除活性。结果表明,酪氨酸的数量、位置和肽的构象对肽的清除率有重要影响(P1、P2、P3和P4清除率分别为34.1±0.8%、45.1±0.9%、58.6±1.3%和48.4±0.96%)。密度泛函理论模拟表明,只有位于˙OH有效扩散距离内的酪氨酸位点才能清除自由基。这些肽对Caco-2细胞不产生细胞毒性。肽处理组可提高谷胱甘肽过氧化物酶(GSH-PX)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)活性,降低丙二醛(MDA)水平。这项工作可能有助于在天然肽类似物的基础上设计出更有活性的抗氧化肽。
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引用次数: 0
Screening of an antimicrobial peptide-TWPAL and its application in hydrogels for wound healing. 抗菌肽twpal的筛选及其在伤口愈合水凝胶中的应用。
Pub Date : 2025-01-15 DOI: 10.1039/d4tb02253j
Huinan Wang, Fengyuan Gao, Muhammad Rafiq, Bing Yu, Qinghai Niu, Hailin Cong

Open wounds are one of the concerns of modern medicine. Early on, before the wound has closed, bacteria can easily enter, leading to bacterial infections. Excipients with antimicrobial effects can greatly facilitate the wound healing process. In this work, we screened and synthesized the antimicrobial peptide Thr-Trp-Pro-Gla-Leu (TWPAL), which has good bacteriostatic effect as well as drug resistance. And by loading it into a hyaluronic acid/gelatin hydrogel, we developed an antimicrobial hydrogel (TWPAL-gel), and by analyzing the results of animal experiments, it was found that this treatment has obvious efficacy in the treatment of animal wound infections, which provides a strong experimental basis for the clinical treatment and an important reference value for the further research on the treatment of diseases. Therefore, a new antimicrobial peptide TWPAL and a hydrogel based on this peptide were developed in this study to provide a comfortable and sterile recovery environment for wound healing, which can be an ideal choice for the treatment of open wounds.

开放性伤口是现代医学关注的问题之一。早期,在伤口闭合之前,细菌很容易进入,导致细菌感染。具有抗菌作用的赋形剂可以大大促进伤口愈合过程。在本研究中,我们筛选并合成了抗菌肽Thr-Trp-Pro-Gla-Leu (TWPAL),该抗菌肽具有良好的抑菌效果和耐药性。并将其装入透明质酸/明胶水凝胶中,研制出抗菌水凝胶(TWPAL-gel),通过动物实验结果分析,发现该治疗方法对动物伤口感染有明显的治疗效果,为临床治疗提供了强有力的实验依据,对进一步研究疾病治疗具有重要的参考价值。因此,本研究开发了一种新型抗菌肽TWPAL及其为基础的水凝胶,为创面愈合提供舒适、无菌的恢复环境,是治疗开放性创面的理想选择。
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引用次数: 0
In situ developed NiCo2O4-Ti3C2Tx nanohybrid towards non-enzymatic electrochemical detection of glucose and hydrogen peroxide. 原位制备了用于葡萄糖和过氧化氢非酶电化学检测的NiCo2O4-Ti3C2Tx纳米杂化物。
Pub Date : 2024-12-23 DOI: 10.1039/d4tb02265c
Devarasu Mohanapriya, Kathavarayan Thenmozhi

Owing to the adverse consequences of excess glucose (Glu) and hydrogen peroxide (H2O2) on humans, it is imperative to develop an electrochemical sensor for detection of these analytes with good selectivity and sensitivity. Herein, a nanohybrid comprising nickel cobaltite nanoparticles (NiCo2O4 NPs) embedded on conductive Ti3C2Tx nanosheets (NSs) has been prudently designed and employed for the electrochemical detection of Glu and H2O2. The developed nanohybrid has been systematically characterized using morphological and spectral techniques, and then immobilized on a glassy carbon electrode (GCE). Under optimized conditions, the developed NiCo2O4-Ti3C2Tx/GCE based electrochemical sensor has demonstrated an impressive analytical response towards Glu and H2O2 with good sensitivity and selectivity. The non-enzymatic sensor has demonstrated a broad linear range from 30 μM to 1.83 mM for Glu, and two linear ranges of 20-100 μM and 100 μM-2.01 mM for H2O2. The sensor has exhibited limits of detection (LOD) of 9 μM and 6 μM with sensitivities of 101.2 μA μM-1 cm-2 and 107.03 μA μM-1 cm-2, respectively, for Glu and H2O2 detection. The impressive analytical performance of the fabricated sensor in terms of linear range, LOD and sensitivity are ascribed to the (i) enhanced conductivity of Ti3C2Tx NSs, (ii) mediated electrocatalytic activity of NiCo2O4 NPs and (iii) large number of catalytically active sites on the NiCo2O4-Ti3C2Tx heterostructure. Notably, the NiCo2O4-Ti3C2Tx/GCE has demonstrated impressive stability and reproducibility, which is mainly due to the in situ uniform growth of NiCo2O4 NPs over Ti3C2Tx NSs.

由于过量葡萄糖(Glu)和过氧化氢(H2O2)对人体的不良影响,开发一种具有良好选择性和灵敏度的电化学传感器检测这些分析物势在必行。本文设计了一种由镍钴酸盐纳米颗粒(NiCo2O4 NPs)包埋在导电Ti3C2Tx纳米片(NSs)上的纳米杂化材料,并将其用于Glu和H2O2的电化学检测。利用形态学和光谱技术对所制备的纳米杂化物进行了系统表征,并将其固定在玻璃碳电极上。在优化条件下,NiCo2O4-Ti3C2Tx/GCE电化学传感器对Glu和H2O2具有良好的灵敏度和选择性。该传感器对Glu的测量线性范围为30 μM ~ 1.83 mM,对H2O2的测量线性范围为20 ~ 100 μM和100 μM ~ 2.01 mM。该传感器对Glu和H2O2的检出限分别为9 μM和6 μM,灵敏度分别为101.2 μA μM-1 cm-2和107.03 μA μM-1 cm-2。该传感器在线性范围、LOD和灵敏度方面的分析性能令人印象深刻,这归功于(i) Ti3C2Tx NSs的电导率增强,(ii) NiCo2O4 NPs的电催化活性介导,(iii) NiCo2O4-Ti3C2Tx异质结构上有大量催化活性位点。值得注意的是,NiCo2O4-Ti3C2Tx/GCE表现出了令人印象深刻的稳定性和再现性,这主要是由于NiCo2O4 NPs在Ti3C2Tx NSs上的原位均匀生长。
{"title":"<i>In situ</i> developed NiCo<sub>2</sub>O<sub>4</sub>-Ti<sub>3</sub>C<sub>2</sub>T<sub><i>x</i></sub> nanohybrid towards non-enzymatic electrochemical detection of glucose and hydrogen peroxide.","authors":"Devarasu Mohanapriya, Kathavarayan Thenmozhi","doi":"10.1039/d4tb02265c","DOIUrl":"https://doi.org/10.1039/d4tb02265c","url":null,"abstract":"<p><p>Owing to the adverse consequences of excess glucose (Glu) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) on humans, it is imperative to develop an electrochemical sensor for detection of these analytes with good selectivity and sensitivity. Herein, a nanohybrid comprising nickel cobaltite nanoparticles (NiCo<sub>2</sub>O<sub>4</sub> NPs) embedded on conductive Ti<sub>3</sub>C<sub>2</sub>T<sub><i>x</i></sub> nanosheets (NSs) has been prudently designed and employed for the electrochemical detection of Glu and H<sub>2</sub>O<sub>2</sub>. The developed nanohybrid has been systematically characterized using morphological and spectral techniques, and then immobilized on a glassy carbon electrode (GCE). Under optimized conditions, the developed NiCo<sub>2</sub>O<sub>4</sub>-Ti<sub>3</sub>C<sub>2</sub>T<sub><i>x</i></sub>/GCE based electrochemical sensor has demonstrated an impressive analytical response towards Glu and H<sub>2</sub>O<sub>2</sub> with good sensitivity and selectivity. The non-enzymatic sensor has demonstrated a broad linear range from 30 μM to 1.83 mM for Glu, and two linear ranges of 20-100 μM and 100 μM-2.01 mM for H<sub>2</sub>O<sub>2</sub>. The sensor has exhibited limits of detection (LOD) of 9 μM and 6 μM with sensitivities of 101.2 μA μM<sup>-1</sup> cm<sup>-2</sup> and 107.03 μA μM<sup>-1</sup> cm<sup>-2</sup>, respectively, for Glu and H<sub>2</sub>O<sub>2</sub> detection. The impressive analytical performance of the fabricated sensor in terms of linear range, LOD and sensitivity are ascribed to the (i) enhanced conductivity of Ti<sub>3</sub>C<sub>2</sub>T<sub><i>x</i></sub> NSs, (ii) mediated electrocatalytic activity of NiCo<sub>2</sub>O<sub>4</sub> NPs and (iii) large number of catalytically active sites on the NiCo<sub>2</sub>O<sub>4</sub>-Ti<sub>3</sub>C<sub>2</sub>T<sub><i>x</i></sub> heterostructure. Notably, the NiCo<sub>2</sub>O<sub>4</sub>-Ti<sub>3</sub>C<sub>2</sub>T<sub><i>x</i></sub>/GCE has demonstrated impressive stability and reproducibility, which is mainly due to the <i>in situ</i> uniform growth of NiCo<sub>2</sub>O<sub>4</sub> NPs over Ti<sub>3</sub>C<sub>2</sub>T<sub><i>x</i></sub> NSs.</p>","PeriodicalId":94089,"journal":{"name":"Journal of materials chemistry. B","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of inner hydrophobicity of dendrimer nanomicelles on biodistribution: a PET imaging study. 树突纳米束内部疏水性对生物分布的影响:PET成像研究。
Pub Date : 2024-12-19 DOI: 10.1039/d4tb01266f
Tom Roussel, Twiany Cruz-Dubois, Beatrice Louis, Erik Laurini, Ling Ding, Laure Balasse, Vincent Nail, Françoise Dignat-George, Suzanne Giorgio, Sabrina Pricl, Benjamin Guillet, Philippe Garrigue, Ling Peng

Self-assembly is a powerful strategy for building nanosystems for biomedical applications. We have recently developed small amphiphilic dendrimers capable of self-assembling into nanomicelles for tumor imaging. In this context, we studied the impact of increased hydrophobicity of the amphiphilic dendrimer on hydrophilic/hydrophobic balance and consequently on the self-assembly and subsequent biodistribution. Remarkably, despite maintaining the exact same surface chemistry, similar zeta potential, and small size, the altered and enlarged hydrophobic component within the amphiphilic dendrimer led to enhanced stability of the self-assembled nanomicelles, with prolonged circulation time and massive accumulation in the liver. This study reveals that even structural alteration within the interior of nanomicelles can dramatically impact biodistribution profiles. This finding highlights the deeper complexity of rational design for nanomedicine and the need to consider factors other than surface charge and chemistry, as well as size, all of which significantly impact the biodistribution of self-assembling nanosystems.

自组装是构建用于生物医学应用的纳米系统的有力策略。我们最近开发了能够自组装成纳米胶束的小两亲性树状大分子,用于肿瘤成像。在这种情况下,我们研究了两亲性树状大分子疏水性的增加对亲疏水平衡的影响,从而对自组装和随后的生物分布的影响。值得注意的是,尽管保持完全相同的表面化学,相似的zeta电位和小尺寸,两亲性树状大分子内疏水成分的改变和扩大导致自组装纳米胶束的稳定性增强,循环时间延长并在肝脏中大量积累。这项研究表明,即使是纳米胶束内部的结构改变也会极大地影响生物分布。这一发现强调了纳米医学合理设计的深层复杂性,以及考虑表面电荷和化学成分以及尺寸以外的因素的必要性,所有这些因素都会显著影响自组装纳米系统的生物分布。
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引用次数: 0
Mitigating intubation stress, mucosa injury, and inflammatory response in nasogastric tube intubation via suppression of the NF-κB signaling pathway by engineering a hydration lubrication coating. 通过设计水合润滑涂层抑制 NF-κB 信号通路,减轻鼻胃管插管时的插管压力、粘膜损伤和炎症反应。
Pub Date : 2024-10-30 DOI: 10.1039/d4tb01171f
Xi Liao, Meng-Han Bai, Yu-Wei Liu, Yu-Qing Wei, Jun-Yang Wang, Zhi-Guo Wang, Rui Hong, Ju-Xiang Gou, Jia-Zhuang Xu, Zhong-Ming Li, Ka Li

Nasogastric tube (NGT) intubation is a common yet critical clinical procedure. However, complications arising from tube friction result in awful pain and morbidity. Here, we report a straightforward surface modification of slender NGT utilizing highly hydrated micelles that were composed of hyaluronic acid and Pluronic. The strong intermolecular hydrogen bonding facilitated the assembly of the micelles on NGT via a one-step dip coating process. The micelle coating conferred excellent hydrophilic, lubrication, anti-protein adhesive, and biocompatible properties. The in vivo efficacy of the micelle coating in alleviating catheterization irritation and mucosal injury was demonstrated using an NGT intubation model of rabbits. More importantly, compared to the paraffin oil coating (the current clinical means), the micelle coating possessed superior capability to reduce the inflammatory reaction caused by NGT intubation. The underlying mechanism was attributed to the suppression of the TLR4-IKBα-NF-κB inflammatory signaling pathway. This work provides a promising solution for developing lubricant medical coatings.

鼻胃管插管(NGT)是一种常见而又关键的临床操作。然而,插管摩擦引起的并发症会导致可怕的疼痛和发病率。在此,我们报告了一种利用由透明质酸和 Pluronic 组成的高水合胶束对细长 NGT 进行直接表面改性的方法。分子间的强氢键促进了胶束通过一步浸涂工艺在 NGT 上的组装。胶束涂层具有优异的亲水性、润滑性、抗蛋白粘附性和生物相容性。使用家兔 NGT 插管模型证明了胶束涂层在减轻导管刺激和粘膜损伤方面的体内疗效。更重要的是,与石蜡油涂层(目前的临床手段)相比,胶束涂层在减轻 NGT 插管引起的炎症反应方面具有更强的能力。其根本机制是抑制了 TLR4-IKBα-NF-κB 炎症信号通路。这项工作为开发润滑性医用涂层提供了一种前景广阔的解决方案。
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引用次数: 0
Rationally designed protein A surface molecularly imprinted magnetic nanoparticles for the capture and detection of Staphylococcus aureus. 合理设计用于捕获和检测金黄色葡萄球菌的 A 蛋白表面分子印迹磁性纳米粒子。
Pub Date : 2024-06-12 DOI: 10.1039/d4tb00392f
Kritika Narula, Soumya Rajpal, Snehasis Bhakta, Senthilguru Kulanthaivel, Prashant Mishra

Staphylococcus aureus (S. aureus), a commensal organism found on the human skin, is commonly associated with nosocomial infections and exhibits virulence mediated by toxins and resistance to antibiotics. The global threat of antibiotic resistance has necessitated antimicrobial stewardship to improve the safe and appropriate use of antimicrobials; hence, there is an urgent demand for the advanced, cost-effective, and rapid detection of specific bacteria. In this regard, we aimed to selectively detect S. aureus using surface molecularly imprinted magnetic nanoparticles templated with a well-known biomarker protein A, specific to S. aureus. Herein, a highly selective surface molecularly imprinted polymeric thin layer was created on ∼250 nm magnetic nanoparticles (MNPs) through the immobilization of protein A to aldehyde functionalized MNPs, followed by monomer polymerization and template washing. This study employs the rational selection of monomers based on their computationally predicted binding affinity to protein A at multiple surface residues. The resulting MIPs from rationally selected monomer combinations demonstrated an imprinting factor as high as ∼5. Selectivity studies revealed MIPs with four-fold higher binding capacity (BC) to protein A than other non-target proteins, such as lysozyme and serum albumin. In addition, it showed significant binding to S. aureus, whereas negligible binding to other non-specific Gram-negative, i.e. Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), and Gram-positive, i.e. Bacillus subtilis (B. subtilis), bacteria. This MIP was employed for the capture and specific detection of fluorescently labeled S. aureus. Quantitative detection was performed using a conventional plate counting technique in a linear detection range of 101-107 bacterial cells. Remarkably, the MIPs also exhibited approximately 100% cell recovery from milk samples spiked with S. aureus (106 CFU mL-1), underscoring its potential as a robust tool for sensitive and accurate bacterial detection in dairy products. The developed MIP exhibiting high affinity and selective binding to protein A finds its potential applications in the magnetic capture and selective detection of protein A as well as S. aureus infections and contaminations.

金黄色葡萄球菌(S. aureus)是一种在人体皮肤上发现的共生有机体,通常与医院内感染有关,并通过毒素和抗生素耐药性表现出毒性。全球抗生素耐药性的威胁要求我们加强抗菌药物管理,以提高抗菌药物使用的安全性和合理性;因此,对先进、经济、快速检测特定细菌的需求十分迫切。在这方面,我们的目标是利用表面分子印迹磁性纳米粒子,以金黄色葡萄球菌的特异性生物标记蛋白 A 为模板,选择性地检测金黄色葡萄球菌。在这里,通过将蛋白质 A 固定在醛官能化的磁性纳米粒子(MNPs)上,然后进行单体聚合和模板清洗,在 ∼250 nm 的磁性纳米粒子(MNPs)上形成了高选择性的表面分子印迹聚合物薄层。本研究根据计算预测的单体与蛋白质 A 在多个表面残基上的结合亲和力,合理选择单体。通过合理选择单体组合得到的 MIPs 的印记因子高达 ∼5。选择性研究显示,与溶菌酶和血清白蛋白等其他非目标蛋白相比,MIPs 与蛋白 A 的结合能力(BC)高出四倍。此外,它对金黄色葡萄球菌有明显的结合力,而对其他非特异性革兰氏阴性菌,即大肠杆菌(E. coli)、铜绿假单胞菌(P. aeruginosa)和革兰氏阳性菌,即枯草杆菌(B. subtilis)的结合力可忽略不计。这种 MIP 用于捕获和特异性检测荧光标记的金黄色葡萄球菌。采用传统的平板计数技术,在 101-107 个细菌细胞的线性检测范围内进行定量检测。值得注意的是,从添加了金黄色葡萄球菌(106 CFU mL-1)的牛奶样品中提取金黄色葡萄球菌细胞,MIPs 的细胞回收率约为 100%,这表明它有潜力成为灵敏、准确地检测乳制品中细菌的有力工具。所开发的 MIP 与蛋白 A 具有高亲和力和选择性结合,有望应用于蛋白 A 以及金黄色葡萄球菌感染和污染的磁捕获和选择性检测。
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引用次数: 0
Looking back, moving forward: protein corona of lipid nanoparticles. 回顾过去,展望未来:脂质纳米粒子的蛋白质电晕。
Pub Date : 2024-06-12 DOI: 10.1039/d4tb00186a
Yue Gao, Yeqi Huang, Chuanyu Ren, Peiwen Chou, Chuanbin Wu, Xin Pan, Guilan Quan, Zhengwei Huang

Lipid nanoparticles (LNPs) are commonly employed for drug delivery owing to their considerable drug-loading capacity, low toxicity, and excellent biocompatibility. Nevertheless, the formation of protein corona (PC) on their surfaces significantly influences the drug's in vivo fate (such as absorption, distribution, metabolism, and elimination) upon administration. PC denotes the phenomenon wherein one or multiple strata of proteins adhere to the external interface of nanoparticles (NPs) or microparticles within the biological milieu, encompassing ex vivo fluids (e.g., serum-containing culture media) and in vivo fluids (such as blood and tissue fluids). Hence, it is essential to claim the PC formation behaviors and mechanisms on the surface of LNPs. This overview provided a comprehensive examination of crucial aspects related to such issues, encompassing time evolution, controllability, and their subsequent impacts on LNPs. Classical studies of PC generation on the surface of LNPs were additionally integrated, and its decisive role in shaping the in vivo fate of LNPs was explored. The mechanisms underlying PC formation, including the adsorption theory and alteration theory, were introduced to delve into the formation process. Subsequently, the existing experimental outcomes were synthesized to offer insights into the research and application facets of PC, and it was concluded that the manipulation of PC held substantial promise in the realm of targeted delivery.

脂质纳米颗粒(LNPs)具有相当大的载药量、低毒性和良好的生物相容性,因此被广泛用于药物输送。然而,脂质纳米粒子表面形成的蛋白质电晕(PC)会严重影响给药后药物在体内的转归(如吸收、分布、代谢和消除)。PC 指的是在生物环境中,包括体外体液(如含血清的培养基)和体内体液(如血液和组织液),纳米颗粒或微粒的外部界面上附着一层或多层蛋白质的现象。因此,了解 LNPs 表面 PC 的形成行为和机制至关重要。本综述全面考察了与这些问题相关的关键方面,包括时间演变、可控性及其对 LNPs 的后续影响。此外,还对 LNPs 表面 PC 生成的经典研究进行了整合,并探讨了 PC 在塑造 LNPs 体内命运方面的决定性作用。介绍了 PC 的形成机制,包括吸附理论和改变理论,以深入探讨 PC 的形成过程。随后,综合现有的实验结果,对 PC 的研究和应用方面提出了见解,并得出结论:操纵 PC 在靶向递送领域大有可为。
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Journal of materials chemistry. B
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