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Optimizing enzyme-responsive polymersomes for protein-based therapies. 为基于蛋白质的疗法优化酶反应聚合体。
Pub Date : 2024-02-01 Epub Date: 2024-01-25 DOI: 10.2217/nnm-2023-0300
Dorian Foster, Alaura Cakley, Jessica Larsen

Aims: Stimuli-responsive polymersomes are promising tools for protein-based therapies, but require deeper understanding and optimization of their pathology-responsive behavior. Materials & methods: Hyaluronic acid (HA)-poly(b-lactic acid) (PLA) polymersomes self-assembled from block copolymers of varying molecular weights of HA were compared for their physical properties, degradation and intracellular behavior. Results: Major results showed increasing enzyme-responsivity associated with decreasing molecular weight. The major formulation differences were as follows: the HA(5 kDa)-PLA formulation exhibited the most pronounced release of encapsulated proteins, while the HA(7 kDa)-PLA formulation showed the most different release behavior from neutral. Conclusion: We have discovered design rules for HA-PLA polymersomes for protein delivery, with lower molecular weight leading to higher encapsulation efficiency, greater release and greater intracellular uptake.

目的:刺激响应型聚合体是一种很有前景的基于蛋白质的治疗工具,但需要对其病理响应行为进行更深入的了解和优化。材料与方法:比较了由不同分子量的透明质酸(HA)嵌段共聚物自组装而成的透明质酸(HA)-聚(b-乳酸)(PLA)聚合体的物理性质、降解和细胞内行为。结果显示主要结果显示,随着分子量的降低,酶反应性也随之增加。主要的配方差异如下:HA(5 kDa)-PLA 配方显示出最明显的包裹蛋白质释放,而 HA(7 kDa)-PLA 配方显示出与中性最不同的释放行为。结论:我们发现了HA-PLA聚合体输送蛋白质的设计规则,分子量越低,封装效率越高,释放量越大,细胞内吸收量也越大。
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引用次数: 0
Radiofrequency driving antitumor effect of graphene oxide-based nanocomposites: a Hill model analysis. 基于氧化石墨烯的纳米复合材料的射频驱动抗肿瘤效应:希尔模型分析。
Pub Date : 2024-02-01 Epub Date: 2023-12-19 DOI: 10.2217/nnm-2023-0312
Melissa S Monteiro, Marina S Mesquita, Leidiane M Garcia, Paulo R Dos Santos, Cássia C de Marangoni de Viveiros, Ronei D da Fonseca, Mary A Xavier, Gabriel Ws de Mendonça, Suélia Srf Rosa, Saulo Lp Silva, Leonardo G Paterno, Paulo C Morais, Sônia N Báo

Aim: This report proposes using the Hill model to assess the benchmark dose, the 50% lethal dose, the cooperativity and the dissociation constant while analyzing cell viability data using nanomaterials to evaluate the antitumor potential while combined with radiofrequency therapy. Materials & methods: A nanocomposite was synthesized (graphene oxide-polyethyleneimine-gold) and the viability was evaluated using two tumor cell lines, namely LLC-WRC-256 and B16-F10. Results: Our findings demonstrated that while the nanocomposite is biocompatible against the LLC-WRC-256 and B16-F10 cancer cell lines in the absence of radiofrequency, the application of radiofrequency enhances the cell toxicity by orders of magnitude. Conclusion: This result points to prospective studies with the tested cell lines using tumor animal models.

目的:本报告建议使用希尔模型评估基准剂量、50%致死剂量、合作性和解离常数,同时分析使用纳米材料的细胞活力数据,以评估与射频疗法相结合的抗肿瘤潜力。材料与方法:合成了一种纳米复合材料(氧化石墨烯-聚乙烯亚胺-金),并使用两种肿瘤细胞系(LLC-WRC-256 和 B16-F10)对其存活率进行了评估。结果显示我们的研究结果表明,虽然在没有射频的情况下,纳米复合材料对 LLC-WRC-256 和 B16-F10 癌细胞株具有生物相容性,但在使用射频的情况下,细胞毒性会以数量级的方式增强。结论这一结果为利用肿瘤动物模型对受测细胞系进行前瞻性研究指明了方向。
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引用次数: 0
Structural features of Prussian Blue-related iron complex - FeT of activity to peroxidate unsaturated fatty acids. 具有过氧化不饱和脂肪酸活性的普鲁士蓝相关铁络合物 FeT 的结构特征。
Pub Date : 2024-02-01 Epub Date: 2024-01-19 DOI: 10.2217/nnm-2023-0206
Małgorzata Lasota, Grzegorz Zemanek, Olga Barczyk-Woźnicka, Anna Misterka, Anna Wiśniewska, Barbara Stopa, Izabela Kościk, Anna Jagusiak, Leszek Konieczny, Irena Roterman

Aim: FeT is a complex of Fe3+, ferricyanide and tartrate, similar in structure to Prussian Blue. Its synthesis was planned to produce a potential antiproliferative drug. Methods: Dynamic light scattering was applied to study nanostructures formed by FeT complexes, while their biological activity was tested following changes in cell proliferation using cultured T24 human bladder cancer cells. Results: The antiproliferative activity of FeT derived from its ability to peroxidate unsaturated fatty acids, which can cause cell death through oxidative stress and/or ferroptosis. FeT molecules associate into drop-like nanostructures in water solutions, between 10-130 nm, which can bind albumin. Conclusion: Fatty acid peroxidation is significantly activated by light. The characteristics and reactivity of FeT represent a prospective application in medicine.

目的:FeT 是一种由 Fe3+、铁氰化物和酒石酸盐组成的复合物,结构与普鲁士蓝相似。计划通过合成这种复合物来生产一种潜在的抗增生药物。研究方法采用动态光散射法研究 FeT 复合物形成的纳米结构,同时利用培养的 T24 人类膀胱癌细胞,根据细胞增殖的变化测试其生物活性。结果显示铁钛的抗增殖活性源于其过氧化不饱和脂肪酸的能力,而不饱和脂肪酸可通过氧化应激和/或铁变态反应导致细胞死亡。铁钛分子在水溶液中结合成水滴状纳米结构,介于 10-130 纳米之间,可与白蛋白结合。结论光能显著激活脂肪酸过氧化反应。FeT的特性和反应性代表了其在医学中的应用前景。
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引用次数: 0
Biocompatibility and proteomic profiling of DMSA-coated iron nanocubes in a human glioblastoma cell line. DMSA 涂层铁纳米立方体在人类胶质母细胞瘤细胞系中的生物相容性和蛋白质组分析。
Pub Date : 2024-02-01 Epub Date: 2024-01-25 DOI: 10.2217/nnm-2023-0304
Marina Ulanova, Lucy Gloag, Chul-Kyu Kim, Andre Bongers, Hong Thien Kim Duong, J Justin Gooding, Richard D Tilley, Perminder S Sachdev, Nady Braidy

Background: Superparamagnetic iron core iron oxide shell nanocubes have previously shown superior performance in magnetic resonance imaging T2 contrast enhancement compared with spherical nanoparticles. Methods: Iron core iron oxide shell nanocubes were synthesized, stabilized with dimercaptosuccinic acid (DMSA-NC) and physicochemically characterized. MRI contrast enhancement and biocompatibility were assessed in vitro. Results: DMSA-NC showed a transverse relaxivity of 122.59 mM-1·s-1 Fe. Treatment with DMSA-NC did not induce cytotoxicity or oxidative stress in U-251 cells, and electron microscopy demonstrated DMSA-NC localization within endosomes and lysosomes in cells following internalization. Global proteomics revealed dysregulation of iron storage, transport, transcription and mRNA processing proteins. Conclusion: DMSA-NC is a promising T2 MRI contrast agent which, in this preliminary investigation, demonstrates favorable biocompatibility with an astrocyte cell model.

背景:与球形纳米粒子相比,超顺磁性铁芯氧化铁壳纳米立方体在磁共振成像 T2 对比增强方面表现出更优越的性能。方法:合成铁芯氧化铁壳纳米立方体,用二巯基丁二酸(DMSA-NC)稳定,并对其进行物理化学表征。在体外对磁共振成像(MRI)对比度增强和生物相容性进行了评估。结果显示DMSA-NC 的横向弛豫度为 122.59 mM-1-s-1 Fe。用 DMSA-NC 处理 U-251 细胞不会引起细胞毒性或氧化应激,电子显微镜显示 DMSA-NC 在细胞内化后定位在内质体和溶酶体中。全局蛋白质组学显示,铁储存、运输、转录和 mRNA 处理蛋白出现失调。结论DMSA-NC 是一种很有前途的 T2 MRI 造影剂,在这项初步研究中,它与星形胶质细胞模型表现出良好的生物相容性。
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引用次数: 0
The application of nanotechnology in kidney transplantation. 纳米技术在肾移植中的应用。
Pub Date : 2024-02-01 Epub Date: 2024-01-26 DOI: 10.2217/nnm-2023-0286
Shengzhou Li, Yiming Chen, Xiangqian Cao, Chenkai Yang, Wei Li, Bing Shen

Kidney transplantation is a crucial treatment option for end-stage renal disease patients, but challenges related to graft function, rejection and immunosuppressant side effects persist. This review highlights the potential of nanotechnology in addressing these challenges. Nanotechnology offers innovative solutions to enhance organ preservation, evaluate graft function, mitigate ischemia-reperfusion injury and improve drug delivery for immunosuppressants. The integration of nanotechnology holds promise for improving outcomes in kidney transplantation.

肾移植是终末期肾病患者的重要治疗选择,但与移植物功能、排斥反应和免疫抑制剂副作用有关的挑战依然存在。本综述强调了纳米技术在应对这些挑战方面的潜力。纳米技术为加强器官保存、评估移植物功能、减轻缺血再灌注损伤和改善免疫抑制剂给药提供了创新解决方案。纳米技术的集成有望改善肾移植的效果。
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引用次数: 0
Novel ligand decorated theranostic zein nanoparticles coloaded with paclitaxel and carbon quantum dots: formulation and optimization. 以紫杉醇和碳量子点为载体的新型配体装饰疗法泽因纳米粒子:配方与优化。
Pub Date : 2024-02-01 Epub Date: 2024-02-02 DOI: 10.2217/nnm-2023-0197
Parth Patel, Anchal Pathak, Keerti Jain

Aim: The present research focused on development and optimization of ligand decorated theranostic nanocarrier encapsulating paclitaxel and carbon quantum dots (CQDs). Methods: CQDs were prepared by microwave-assisted pyrolysis and were characterized for particle size and fluorescence behavior. Ligand decorated zein nanoparticles, coloaded with paclitaxel and CQDs, were formulated using a one-step nanoprecipitation method and optimized for various process parameters. Results: Particle size for coated and uncoated nanoparticles was 90.16 ± 1.65 and 179.26 ± 3.61 nm, respectively, and entrapment efficiency was >80%. The circular dichroism spectroscopy showed zein retained its secondary structure and release study showed biphasic release behavior. Conclusion: The prepared theranostic nanocarrier showed optimal fluorescence and desired release behavior without altering the secondary structure of zein.

目的:本研究的重点是开发和优化配体装饰的、封装紫杉醇和碳量子点(CQDs)的治疗纳米载体。研究方法:通过微波辅助热解法制备碳量子点,并对其粒度和荧光行为进行表征。采用一步纳米沉淀法制备了配体装饰的泽因纳米颗粒,其中添加了紫杉醇和 CQDs,并对各种工艺参数进行了优化。结果显示有包覆和无包覆纳米粒子的粒径分别为 90.16 ± 1.65 nm 和 179.26 ± 3.61 nm,夹带效率大于 80%。圆二色性光谱显示玉米素保留了其二级结构,释放研究显示了双相释放行为。结论在不改变玉米素二级结构的情况下,制备的治疗纳米载体显示出最佳的荧光和理想的释放行为。
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引用次数: 0
Can animal models help to explore functions of nanoparticles in health and diseases? 动物模型能帮助探索纳米颗粒在健康和疾病中的功能吗?
Pub Date : 2024-02-01 Epub Date: 2023-12-07 DOI: 10.2217/nnm-2023-0323
Caijuan Dong, Lijun Shang
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引用次数: 0
Elevated glutathione in researchers exposed to engineered nanoparticles due to potential adaptation to oxidative stress. 由于对氧化应激的潜在适应,暴露于工程纳米粒子的研究人员体内谷胱甘肽升高。
Pub Date : 2024-02-01 Epub Date: 2024-01-26 DOI: 10.2217/nnm-2023-0207
Pavlina Klusackova, Lucie Lischkova, Viktoriia Kolesnikova, Tomas Navratil, Stepanka Vlckova, Zdenka Fenclova, Jaroslav Schwarz, Jakub Ondracek, Lucie Ondrackova, Martin Kostejn, Stepanka Dvorackova, Andrea Rossnerova, Miroslav Pohanka, Pavel Bradna, Vladimir Zdimal, Daniela Pelclova

Aim: To find a practical biomonitoring method for researchers exposed to nanoparticles causing oxidative stress. Methods: In a continuation of a study in 2016-2018, biological samples (plasma, urine and exhaled breath condensate [EBC]) were collected in 2019-2020 from 43 researchers (13.8 ± 3.0 years of exposure) and 45 controls. Antioxidant status was assessed using glutathione (GSH) and ferric-reducing antioxidant power, while oxidative stress was measured as thiobarbituric acid reactive substances, all using spectrophotometric methods. Researchers' personal nanoparticle exposure was monitored. Results: Plasma GSH was elevated in researchers both before and after exposure (p < 0.01); postexposure plasma GSH correlated with nanoparticle exposure, and GSH in EBC increased. Conclusion: The results suggest adaptation to chronic exposure to nanoparticles, as monitored by plasma and EBC GSH.

目的:为暴露于纳米粒子导致氧化应激的研究人员找到一种实用的生物监测方法。方法:作为 2016-2018 年研究的延续,2019-2020 年收集了 43 名研究人员(暴露年限为 13.8 ± 3.0 年)和 45 名对照组的生物样本(血浆、尿液和呼出气体冷凝物 [EBC])。使用谷胱甘肽(GSH)和铁还原抗氧化能力评估抗氧化状态,使用硫代巴比妥酸活性物质测量氧化应激,所有方法均采用分光光度法。对研究人员的个人纳米粒子暴露进行了监测。结果研究人员在接触纳米粒子前后血浆 GSH 都有所升高(p 结论:研究人员在接触纳米粒子前后血浆 GSH 都有所升高:结果表明,通过监测血浆和 EBC GSH,研究人员可以适应长期接触纳米粒子。
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引用次数: 0
Neuritogenic activity of metal nanoparticles. 金属纳米粒子的致神经细胞活性。
Pub Date : 2024-02-01 Epub Date: 2024-01-12 DOI: 10.2217/nnm-2023-0297
Sudipta Saha, Sanchita Tripathy, Chitta Ranjan Patra
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引用次数: 0
Lipid-based nanomedicines for the treatment of bacterial respiratory infections: current state and new perspectives. 治疗细菌性呼吸道感染的脂基纳米药物:现状与新前景。
Pub Date : 2024-02-01 Epub Date: 2024-01-25 DOI: 10.2217/nnm-2023-0243
Eva María Arroyo-Urea, María Lázaro-Díez, Junkal Garmendia, Fernando Herranz, Ana González-Paredes

The global threat posed by antimicrobial resistance demands urgent action and the development of effective drugs. Lower respiratory tract infections remain the deadliest communicable disease worldwide, often challenging to treat due to the presence of bacteria that form recalcitrant biofilms. There is consensus that novel anti-infectives with reduced resistance compared with conventional antibiotics are needed, leading to extensive research on innovative antibacterial agents. This review explores the recent progress in lipid-based nanomedicines developed to counteract bacterial respiratory infections, especially those involving biofilm growth; focuses on improved drug bioavailability and targeting and highlights novel strategies to enhance treatment efficacy while emphasizing the importance of continued research in this dynamic field.

抗菌药耐药性对全球构成的威胁要求我们采取紧急行动,开发有效的药物。下呼吸道感染仍然是全球最致命的传染病,由于细菌形成顽固的生物膜,治疗起来往往具有挑战性。与传统抗生素相比,新型抗感染药物的耐药性更低,这一点已达成共识,从而引发了对创新抗菌剂的广泛研究。这篇综述探讨了为应对细菌呼吸道感染(尤其是涉及生物膜生长的感染)而开发的脂基纳米药物的最新进展;重点关注改进药物的生物利用度和靶向性,并着重介绍了提高治疗效果的新策略,同时强调了在这一充满活力的领域继续开展研究的重要性。
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引用次数: 0
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Nanomedicine (London, England)
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