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Improved pharmacokinetics and enhanced efficacy of the vancomycin derivative FU002 using a liposomal nanocarrier 利用脂质体纳米载体改善万古霉素衍生物 FU002 的药代动力学并提高其疗效
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-12-27 DOI: 10.1016/j.nano.2023.102731
Julia Werner MSc , Florian Umstätter PhD , Tobias Hertlein PhD , Barbro Beijer PhD , Christian Kleist PhD , Eric Mühlberg MSc , Stefan Zimmermann MD , Uwe Haberkorn MD , Knut Ohlsen PhD , Gert Fricker PhD , Walter Mier PhD , Philipp Uhl PhD

Antibiotic resistance still represents a global health concern which diminishes the pool of effective antibiotics. With the vancomycin derivative FU002, we recently reported a highly potent substance active against Gram-positive bacteria with the potential to overcome vancomycin resistance. However, the translation of its excellent antimicrobial activity into clinical efficiency could be hampered by its rapid elimination from the blood stream. To improve its pharmacokinetics, we encapsulated FU002 in PEGylated liposomes. For PEG-liposomal FU002, no relevant cytotoxicity on liver, kidney and red blood cells was observed. Studies in Wistar rats revealed a significantly prolonged blood circulation of the liposomal antibiotic. In microdilution assays it could be demonstrated that encapsulation does not diminish the antimicrobial activity against staphylococci and enterococci. Highlighting its great potency, liposomal FU002 exhibited a superior therapeutic efficacy when compared to the free form in a Galleria mellonella larvae infection model.

抗生素耐药性仍然是一个全球健康问题,它削弱了有效抗生素的储备。最近,我们报道了万古霉素衍生物 FU002,它是一种对革兰氏阳性细菌非常有效的物质,具有克服万古霉素耐药性的潜力。然而,由于 FU002 能迅速从血流中排出,因此无法将其出色的抗菌活性转化为临床疗效。为了改善其药代动力学,我们将 FU002 封装在 PEG 脂质体中。PEG 脂质体 FU002 对肝、肾和红细胞没有相关的细胞毒性。对 Wistar 大鼠的研究表明,脂质体抗生素的血液循环时间明显延长。在微量稀释试验中,可以证明脂质体不会降低对葡萄球菌和肠球菌的抗菌活性。与游离态相比,脂质体 FU002 在灰飞虱幼虫感染模型中表现出更高的疗效,这凸显了其强大的功效。
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引用次数: 0
Membrane cholesterol enrichment and folic acid functionalization lead to increased accumulation of erythrocyte-derived optical nano-constructs within the ovarian intraperitoneal tumor implants in mice 膜胆固醇富集和叶酸功能化导致小鼠卵巢腹腔内肿瘤植入物中红细胞来源的光学纳米构建物的积累增加
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-12-05 DOI: 10.1016/j.nano.2023.102728
Chi-Hua Lee PhD , Jenny Mac PhD , Taylor Hanley PhD , Shamima Zaman MS , Raviraj Vankayala PhD , Bahman Anvari PhD

Cytoreductive surgery remains as the gold standard to treat ovarian cancer, but with limited efficacy since not all tumors can be intraoperatively visualized for resection. We have engineered erythrocyte-derived nano-constructs that encapsulate the near infrared (NIR) fluorophore, indocyanine green (ICG), as optical probes for NIR fluorescence imaging of ovarian tumors. Herein, we have enriched the membrane of these nano-constructs with cholesterol, and functionalized their surface with folic acid (FA) to target the folate receptor-α. Using a mouse model, we show that the average fraction of the injected dose per tumor mass for nano-constructs with both membrane cholesterol enrichment and FA functionalization was ~ sixfold higher than non-encapsulated ICG, ~ twofold higher than nano-constructs enriched with cholesterol alone, and 33 % higher than nano-constructs with only FA functionalization at 24-h post-injection. These results suggest that erythrocyte-derived nano-constructs containing both cholesterol and FA present a platform for improved fluorescence imaging of ovarian tumors.

细胞减少手术仍然是治疗卵巢癌的金标准,但由于并非所有肿瘤都能术中可见切除,其疗效有限。我们设计了红细胞衍生的纳米结构,封装近红外(NIR)荧光团,吲哚菁绿(ICG),作为近红外荧光成像卵巢肿瘤的光学探针。在这里,我们用胆固醇丰富了这些纳米结构的膜,并在其表面用叶酸(FA)功能化,以靶向叶酸受体-α。通过小鼠模型,我们发现,在注射后24小时,具有膜胆固醇富集和FA功能化的纳米构建物的每个肿瘤块的平均注射剂量比未包封的ICG高6倍,比仅富含胆固醇的纳米构建物高2倍,比仅具有FA功能化的纳米构建物高33. %。这些结果表明,含有胆固醇和FA的红细胞衍生纳米结构为改善卵巢肿瘤的荧光成像提供了一个平台。
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引用次数: 0
Integrating osteoimmunology and nanoparticle-based drug delivery systems for enhanced fracture healing 整合骨免疫学和纳米颗粒为基础的药物输送系统,促进骨折愈合。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-12-04 DOI: 10.1016/j.nano.2023.102727
Baixue Xiao PhD , Emmanuela Adjei-Sowah MS , Danielle S.W. Benoit PhD

Fracture healing is a complex interplay of molecular and cellular mechanisms lasting from days to weeks. The inflammatory phase is the first stage of fracture healing and is critical in setting the stage for successful healing. There has been growing interest in exploring the role of the immune system and novel therapeutic strategies, such as nanoparticle drug delivery systems in enhancing fracture healing. Advancements in nanotechnology have revolutionized drug delivery systems to the extent that they can modulate immune response during fracture healing by leveraging unique physiochemical properties. Therefore, understanding the intricate interactions between nanoparticle-based drug delivery systems and the immune response, specifically macrophages, is essential for therapeutic efficacy. This review provides a comprehensive overview of the relationship between the immune system and nanoparticles during fracture healing. Specifically, we highlight the influence of nanoparticle characteristics, such as size, surface properties, and composition, on macrophage activation, polarization, and subsequent immune responses.

Impact statement

This review provides valuable insights into the interplay between fracture healing, the immune system, and nanoparticle-based drug delivery systems. Understanding nanoparticle-macrophage interactions can advance the development of innovative therapeutic approaches to enhance fracture healing, improve patient outcomes, and pave the way for advancements in regenerative medicine.

骨折愈合是一个复杂的相互作用的分子和细胞机制持续数天至数周。炎症期是骨折愈合的第一阶段,是为骨折成功愈合奠定基础的关键阶段。人们对探索免疫系统和新型治疗策略的作用越来越感兴趣,例如纳米颗粒药物输送系统在促进骨折愈合方面的作用。纳米技术的进步已经彻底改变了药物输送系统,它们可以通过利用独特的物理化学特性来调节骨折愈合过程中的免疫反应。因此,了解基于纳米颗粒的药物传递系统与免疫反应(特别是巨噬细胞)之间复杂的相互作用对于治疗效果至关重要。本文综述了在骨折愈合过程中免疫系统和纳米颗粒之间的关系。具体来说,我们强调纳米颗粒的特性,如大小、表面性质和组成,对巨噬细胞活化、极化和随后的免疫反应的影响。影响声明:本综述为骨折愈合、免疫系统和基于纳米颗粒的药物传递系统之间的相互作用提供了有价值的见解。了解纳米颗粒-巨噬细胞的相互作用可以促进创新治疗方法的发展,以增强骨折愈合,改善患者的治疗效果,并为再生医学的进步铺平道路。
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引用次数: 0
Customizing biomimetic surface attributes of dendritic lipopeptide nanoplatforms for extended circulation 定制树枝状脂肽纳米平台的生物仿生表面属性,以延长流通时间。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-12-03 DOI: 10.1016/j.nano.2023.102726
Jingjing Wei MSc , Yin Zhou MSc , Yiyan He PhD , Wentao Zhao MSc , Zhiqiang Luo PhD , Jian Yang PhD , Hongli Mao PhD , Zhongwei Gu MSc (Professor)

The pressing demand for innovative approaches to create delivery systems with heightened drug loading and prolonged circulation has spurred numerous efforts, yielding some successes but accompanied by constraints. Our study proposes employing dendritic lipopeptide with precisely balanced opposing charges to extend blood residency for biomimetic nanoplatforms. Neutrally mixed-charged zwitterionic nanoparticles (NNPs) achieved a notable 19 % simvastatin loading content and kept stable even after one-month storage at 4 °C. These nanoplatforms demonstrated low cytotoxicity in NIH-3T3 and L02 cells and negligible hemolysis (<5 %). NNPs inhibited protein adhesion (>95 %) from positively and negatively charged sources through surface hydration. In comparison to positively charged CNPs, NNPs demonstrated an 86 % decrease in phagocytic rate by BMDMs, highlighting their efficacy. Importantly, NNPs showed prolonged circulation compared to CNPs and free simvastatin. These findings highlight the potential of this biomimetic nanoplatform for future therapeutic applications with enhanced drug loading and circulation traits.

人们迫切要求采用创新方法来创建具有更高的药物负荷和更长的循环时间的给药系统,这促使人们做出了许多努力,取得了一些成功,但也存在一些限制。我们的研究提出利用具有精确平衡的对立电荷的树枝状脂肽来延长仿生纳米平台在血液中的停留时间。中性混合电荷的齐聚物纳米颗粒(NNPs)的辛伐他汀载量达到了显著的 19%,并且在 4 °C 下储存一个月后仍保持稳定。这些纳米平台在 NIH-3T3 和 L02 细胞中的细胞毒性很低,通过表面水合作用,正负电荷源的溶血率(95%)可忽略不计。与带正电荷的 CNPs 相比,NNPs 使 BMDMs 的吞噬率降低了 86%,从而突显了其功效。重要的是,与 CNPs 和游离辛伐他汀相比,NNPs 的循环时间更长。这些发现凸显了这种生物仿生纳米平台在未来治疗应用中的潜力,它具有更强的药物负载和循环特性。
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引用次数: 0
Defined covalent attachment of three cancer drugs to DNA origami increases cytotoxicity at nanomolar concentration 三种癌症药物在DNA折纸上的共价附着在纳米摩尔浓度下增加细胞毒性。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-11-24 DOI: 10.1016/j.nano.2023.102722
Natalia Navarro MSc , Anna Aviñó PhD , Òscar Domènech PhD , Jordi H. Borrell PhD , Ramon Eritja PhD , Carme Fàbrega PhD

DNA nanostructures have captured great interest as drug delivery vehicles for cancer therapy. Despite rapid progress in the field, some hurdles, such as low cellular uptake, low tissue specificity or ambiguous drug loading, remain unsolved. Herein, well-known antitumor drugs (doxorubicin, auristatin, and floxuridine) were site-specifically incorporated into DNA nanostructures, demonstrating the potential advantages of covalently linking drug molecules via structural staples instead of incorporating the drugs by noncovalent binding interactions. The covalent strategy avoids critical issues such as an unknown number of drug-DNA binding events and premature drug release. Moreover, covalently modified origami offers the possibility of precisely incorporating several synergetic antitumor drugs into the DNA nanostructure at a predefined molar ratio and to control the exact spatial orientation of drugs into DNA origami. Additionally, DNA-based nanoscaffolds have been reported to have a low intracellular uptake. Thus, two cellular uptake enhancing mechanisms were studied: the introduction of folate units covalently linked to DNA origami and the transfection of DNA origami with Lipofectamine. Importantly, both methods increased the internalization of DNA origami into HTB38 and HCC2998 colorectal cancer cells and produced greater cytotoxic activity when the DNA origami incorporated antiproliferative drugs. The results here present a successful and conceptually distinct approach for the development of DNA-based nanostructures as drug delivery vehicles, which can be considered an important step towards the development of highly precise nanomedicines.

DNA纳米结构作为癌症治疗的药物传递载体引起了人们的极大兴趣。尽管该领域进展迅速,但一些障碍,如低细胞摄取、低组织特异性或不明确的药物负荷,仍未得到解决。在本研究中,众所周知的抗肿瘤药物(阿霉素、奥斯特丁和氟尿定)被位点特异性地结合到DNA纳米结构中,证明了通过结构钉共价连接药物分子而不是通过非共价结合相互作用结合药物的潜在优势。共价策略避免了诸如未知数量的药物- dna结合事件和药物过早释放等关键问题。此外,共价修饰的折纸提供了将几种协同抗肿瘤药物以预定的摩尔比精确地结合到DNA纳米结构中的可能性,并控制药物进入DNA折纸的精确空间方向。此外,据报道,基于dna的纳米支架具有较低的细胞内摄取。因此,研究了两种细胞摄取增强机制:引入与DNA折纸共价连接的叶酸单位和用Lipofectamine转染DNA折纸。重要的是,这两种方法都增加了DNA折纸在HTB38和HCC2998结肠直肠癌细胞中的内化,并且当DNA折纸加入抗增殖药物时,产生了更大的细胞毒活性。该研究结果为开发基于dna的纳米结构作为药物递送载体提供了一种成功的、概念上独特的方法,这可以被认为是开发高精度纳米药物的重要一步。
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引用次数: 0
Monoclonal antibody-navigated carbon-encapsulated iron nanoparticles used for MRI-based tracking integrin receptors in murine melanoma 单克隆抗体导航碳包裹铁纳米颗粒用于小鼠黑色素瘤中基于mri的整合素受体跟踪。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-11-24 DOI: 10.1016/j.nano.2023.102721
Magdalena Bamburowicz-Klimkowska PhD , Michal Bystrzejewski PhD, DSc , Artur Kasprzak PhD, DSc , Andrzej Cieszanowski MD, PhD, Prof , Ireneusz P. Grudzinski PhD, DSc, Prof

Integrin beta-3 is a cell adhesion molecule that mediate cell-to-cell and cell-to-extracellular matrix communication. The major goal of this study was to explore melanoma cells (B16F10) based upon specific direct targeting of the β3 subunit (CD61) in the integrin αvβ3 receptor using carbon-encapsulated iron nanoparticles decorated with monoclonal antibodies (Fe@C-CONH-anti-CD61 and Fe@C-(CH2)2-CONH-anti-CD61). Both melanoma cells treated with nanoparticles as well as C57BL/6 mice bearing syngeneic B16-F10 tumors intravenously injected with nanoparticles were tested in preclinical MRI studies. The as-synthesized carbon-encapsulated iron nanoparticles functionalized with CD61 monoclonal antibodies have been successfully used as a novel targeted contrast agent for MRI-based tracking melanoma cells expressing the β3 subunit of the integrin αvβ3 receptor.

整合素-3是一种细胞粘附分子,介导细胞间和细胞外基质的通讯。本研究的主要目的是利用碳包覆铁纳米颗粒修饰单克隆抗体(Fe@C-CONH-anti-CD61和Fe@C-(CH2)2-CONH-anti-CD61),特异性直接靶向整合素αvβ3受体中β3亚基(CD61),探索黑色素瘤细胞(B16F10)。在临床前MRI研究中,用纳米颗粒处理的黑色素瘤细胞以及静脉注射纳米颗粒的携带同源B16-F10肿瘤的C57BL/6小鼠进行了测试。经CD61单克隆抗体修饰的碳包覆铁纳米颗粒已被成功用作一种新型靶向造影剂,用于基于mri追踪表达整合素αvβ3受体β3亚基的黑色素瘤细胞。
{"title":"Monoclonal antibody-navigated carbon-encapsulated iron nanoparticles used for MRI-based tracking integrin receptors in murine melanoma","authors":"Magdalena Bamburowicz-Klimkowska PhD ,&nbsp;Michal Bystrzejewski PhD, DSc ,&nbsp;Artur Kasprzak PhD, DSc ,&nbsp;Andrzej Cieszanowski MD, PhD, Prof ,&nbsp;Ireneusz P. Grudzinski PhD, DSc, Prof","doi":"10.1016/j.nano.2023.102721","DOIUrl":"10.1016/j.nano.2023.102721","url":null,"abstract":"<div><p><span><span><span>Integrin beta-3 is a </span>cell adhesion molecule<span> that mediate cell-to-cell and cell-to-extracellular matrix communication. The major goal of this study was to explore melanoma cells (B16F10) based upon specific direct targeting of the β3 subunit (CD61) in the integrin αvβ3 receptor using carbon-encapsulated iron </span></span>nanoparticles<span> decorated with monoclonal antibodies (Fe@C-CONH-anti-CD61 and Fe@C-(CH</span></span><sub>2</sub>)<sub>2</sub><span><span>-CONH-anti-CD61). Both melanoma cells treated with nanoparticles as well as C57BL/6 mice bearing syngeneic B16-F10 tumors intravenously injected with nanoparticles were tested in preclinical MRI studies. The as-synthesized carbon-encapsulated iron nanoparticles functionalized with </span>CD61 monoclonal antibodies have been successfully used as a novel targeted contrast agent for MRI-based tracking melanoma cells expressing the β3 subunit of the integrin αvβ3 receptor.</span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"55 ","pages":"Article 102721"},"PeriodicalIF":5.4,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhanced cartilage regeneration by icariin and mesenchymal stem cell-derived extracellular vesicles combined in alginate-hyaluronic acid hydrogel 海藻酸-透明质酸水凝胶结合淫羊藿苷和间充质干细胞来源的细胞外囊泡促进软骨再生。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-11-23 DOI: 10.1016/j.nano.2023.102723
Shuyi Li MSc , Qian Yuan MSc , Minghui Yang BSc , Xinyi Long BSc , Jianwu Sun MSc , Xin Yuan BSc , Lang Liu BSc , Wanting Zhang BSc , Quanjiang Li BSc , Zhujie Deng BSc , Rui Tian BSc , Renhao Xu BSc , Lingna Xie MSc , Jingna Yuan BSc , Yue He MD , Yi Liu MD , Hongmei Liu MD , Zhengqiang Yuan PhD

Objective

Osteoarthritis (OA) is characterized by progressive cartilage degeneration and absence of curative therapies. Therefore, more efficient therapies are compellingly needed. Both mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) and Icariin (ICA) are promising for repair of cartilage defect. This study proposes that ICA may be combined to potentiate the cartilage repair capacity of MSC-EVs.

Materials and methods

MSC-EVs were isolated from sodium alginate (SA) and hyaluronic acid (HA) composite hydrogel (SA-HA) cell spheroid culture. EVs and ICA were combined in SA-HA hydrogel to test therapeutic efficacy on cartilage defect in vivo.

Results

EVs and ICA were synergistic for promoting both proliferation and migration of MSCs and inflammatory chondrocytes. The combination therapy led to strikingly enhanced repair on cartilage defect in rats, with mechanisms involved in the concomitant modulation of both cartilage degradation and synthesis makers.

Conclusion

The MSC-EVs-ICA/SA-HA hydrogel potentially constitutes a novel therapy for cartilage defect in OA.

目的:骨关节炎(OA)的特点是进行性软骨变性和缺乏根治性治疗。因此,迫切需要更有效的治疗方法。间充质干细胞(MSCs)衍生的细胞外囊泡(EVs)和淫羊藿苷(ICA)在软骨缺损的修复中都有很好的应用前景。本研究提出ICA可能联合增强msc - ev的软骨修复能力。材料和方法:从海藻酸钠(SA)和透明质酸(HA)复合水凝胶(SA-HA)细胞球体培养中分离出msc - ev。采用SA-HA水凝胶联合ev和ICA,观察其对软骨缺损的体内治疗效果。结果:EVs和ICA在促进MSCs和炎性软骨细胞增殖和迁移方面具有协同作用。联合治疗显著增强了大鼠软骨缺损的修复,其机制涉及软骨降解和合成因子的伴随调节。结论:msc - ev - ica /SA-HA水凝胶是一种治疗骨性关节炎软骨缺损的新方法。
{"title":"Enhanced cartilage regeneration by icariin and mesenchymal stem cell-derived extracellular vesicles combined in alginate-hyaluronic acid hydrogel","authors":"Shuyi Li MSc ,&nbsp;Qian Yuan MSc ,&nbsp;Minghui Yang BSc ,&nbsp;Xinyi Long BSc ,&nbsp;Jianwu Sun MSc ,&nbsp;Xin Yuan BSc ,&nbsp;Lang Liu BSc ,&nbsp;Wanting Zhang BSc ,&nbsp;Quanjiang Li BSc ,&nbsp;Zhujie Deng BSc ,&nbsp;Rui Tian BSc ,&nbsp;Renhao Xu BSc ,&nbsp;Lingna Xie MSc ,&nbsp;Jingna Yuan BSc ,&nbsp;Yue He MD ,&nbsp;Yi Liu MD ,&nbsp;Hongmei Liu MD ,&nbsp;Zhengqiang Yuan PhD","doi":"10.1016/j.nano.2023.102723","DOIUrl":"10.1016/j.nano.2023.102723","url":null,"abstract":"<div><h3>Objective</h3><p><span>Osteoarthritis<span> (OA) is characterized by progressive cartilage degeneration and absence of curative therapies. Therefore, more efficient therapies are compellingly needed. Both </span></span>mesenchymal stem cells<span> (MSCs)-derived extracellular vesicles (EVs) and Icariin (ICA) are promising for repair of cartilage defect. This study proposes that ICA may be combined to potentiate the cartilage repair capacity of MSC-EVs.</span></p></div><div><h3>Materials and methods</h3><p><span>MSC-EVs were isolated from sodium alginate<span> (SA) and hyaluronic acid (HA) </span></span>composite hydrogel<span> (SA-HA) cell spheroid culture. EVs and ICA were combined in SA-HA hydrogel to test therapeutic efficacy on cartilage defect in vivo.</span></p></div><div><h3>Results</h3><p>EVs and ICA were synergistic for promoting both proliferation and migration of MSCs and inflammatory chondrocytes. The combination therapy led to strikingly enhanced repair on cartilage defect in rats, with mechanisms involved in the concomitant modulation of both cartilage degradation and synthesis makers.</p></div><div><h3>Conclusion</h3><p>The MSC-EVs-ICA/SA-HA hydrogel potentially constitutes a novel therapy for cartilage defect in OA.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"55 ","pages":"Article 102723"},"PeriodicalIF":5.4,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intrinsic variability of fluorescence calibrators impacts the assignment of MESF or ERF values to nanoparticles and extracellular vesicles by flow cytometry 荧光校准器的内在可变性影响了流式细胞术对纳米颗粒和细胞外囊泡的MESF或ERF值的分配。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-11-23 DOI: 10.1016/j.nano.2023.102720
Estefanía Lozano-Andrés PhD , Tina Van Den Broeck PhD , Lili Wang PhD , Majid Mehrpouyan PhD , Ye Tian PhD , Xiaomei Yan PhD , Ger J.A. Arkesteijn PhD , Marca H.M. Wauben PhD

Flow cytometry allows to characterize nanoparticles (NPs) and extracellular vesicles (EVs) but results are often expressed in arbitrary units of fluorescence. We evaluated the precision and accuracy of molecules of equivalent soluble fluorophores (MESF) beads for calibration of NPs and EVs. Firstly, two FITC-MESF bead sets, 2 and 6 um in size, were measured on three flow cytometers. We showed that arbitrary units could not be compared between instruments but after calibration, comparable FITC MESF units were achieved. However, the two calibration bead sets displayed varying slopes that were consistent across platforms.

Further investigation revealed that the intrinsic uncertainty related to the MESF beads impacts the robust assignment of values to NPs and EVs based on extrapolation into the dim fluorescence range. Similar variations were found with PE MESF calibration.

Therefore, the same calibration materials and numbers of calibration points should be used for reliable comparison of submicron sized particles.

流式细胞术可以表征纳米颗粒(NPs)和细胞外囊泡(ev),但结果通常以任意单位的荧光表达。我们评估了等效可溶性荧光团(MESF)微球分子的精度和准确性,用于NPs和ev的校准。首先,在三台流式细胞仪上测量两个FITC-MESF头组,大小分别为2 um和6 um。我们发现任意单位不能在仪器之间进行比较,但在校准后,可以获得可比较的FITC MESF单位。然而,两个校准头组显示不同的斜度,在各个平台上是一致的。进一步的研究表明,与MESF珠相关的固有不确定性影响了基于外推到微弱荧光范围的np和ev值的稳健分配。在PE MESF校准中也发现了类似的变化。因此,为了对亚微米级颗粒进行可靠的比较,应使用相同的校准材料和校准点的数量。
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引用次数: 0
Ready-to-use nanopore platform for label-free small molecule quantification: Ethanolamine as first example 现成的纳米孔平台,用于无标记的小分子定量:乙醇胺为第一个例子。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-11-23 DOI: 10.1016/j.nano.2023.102724
Isabel Quint MSc , Jonathan Simantzik MSc , Lars Kaiser PhD , Stefan Laufer PhD , Rene' Csuk PhD , David Smith PhD , Matthias Kohl PhD , Hans-Peter Deigner PhD

In recent decades, nanopores have become a promising diagnostic tool. Protein and solid-state nanopores are increasingly used for both RNA/DNA sequencing and small molecule detection. The latter is of great importance, as their detection is difficult or expensive using available methods such as HPLC or LC-MS. DNA aptamers are an excellent detection element for sensitive and specific detection of small molecules. Herein, a method for quantifying small molecules using a ready-to-use sequencing platform is described.

Taking ethanolamine as an example, a strand displacement assay is developed in which the target-binding aptamer is displaced from the surface of magnetic particles by ethanolamine. Non-displaced aptamer and thus the ethanolamine concentration are detected by the nanopore system and can be quantified in the micromolar range using our in-house developed analysis software. This method is thus the first to describe a label-free approach for the detection of small molecules in a protein nanopore system.

近几十年来,纳米孔已成为一种很有前途的诊断工具。蛋白质和固态纳米孔越来越多地用于RNA/DNA测序和小分子检测。后者非常重要,因为使用HPLC或LC-MS等现有方法检测它们困难或昂贵。DNA适体是一种灵敏、特异的小分子检测元件。本文描述了一种利用即用型测序平台定量小分子的方法。以乙醇胺为例,开发了一种链置换法,其中目标结合适体被乙醇胺从磁性颗粒表面置换。通过纳米孔系统检测非位移适配体和乙醇胺浓度,并可以使用我们内部开发的分析软件在微摩尔范围内进行量化。因此,该方法首次描述了一种用于检测蛋白质纳米孔系统中的小分子的无标记方法。
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引用次数: 0
Dual-targeted nanoparticles with removing ROS inside and outside mitochondria for acute kidney injury treatment 去除线粒体内外活性氧的双靶向纳米颗粒治疗急性肾损伤。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-11-23 DOI: 10.1016/j.nano.2023.102725
Mengmeng Zhao MD , Jialing Guo PhD , Chaoying Tian MD , Mei Yan MD , Yingying Zhou MD , Chenxin Liu MD , Mengxue Pang MD , Bin Du Prof , Genyang Cheng Prof

Mitochondrial oxidative stress and inflammation are the main pathological features of acute kidney injury (AKI). However, systemic toxicity of anti-inflammatory drugs and low bioavailability of antioxidants limit the treatment of AKI. Here, the lipid micelle nanosystem modified with l-serine was designed to improve treatment of AKI. The micelle kernels coating the antioxidant drug 4-carboxybutyl triphenylph-osphine bromide-modified curcumin (Cur-TPP) and quercetin (Que). In the cisplatin (CDDP)-induced AKI model, the nanosystem protected mitochondrial structure and improved renal function. Compared to mono-targeted group, the mitochondrial ROS content of renal tubular epithelial cells acting in the dual-target group decreased about 1.66-fold in vitro, serum creatinine (Scr) and urea nitrogen (BUN) levels were reduced by 1.5 and 1.2 mmol/L in vivo, respectively. Mechanistic studies indicated that the nanosystem inhibited the inflammatory response by interfering with the NF-κB and Nrf2 pathways. This study provides an efficient and low-toxicity strategy for AKI therapy.

线粒体氧化应激和炎症是急性肾损伤(AKI)的主要病理特征。然而,抗炎药物的全身毒性和抗氧化剂的低生物利用度限制了AKI的治疗。本研究设计了l-丝氨酸修饰的脂质胶束纳米系统,以改善AKI的治疗。用胶束包覆抗氧化药物4-羧基丁基三苯基溴化膦改性姜黄素(Cur-TPP)和槲皮素(Que)。在顺铂(CDDP)诱导的AKI模型中,纳米系统保护线粒体结构并改善肾功能。与单靶点组相比,双靶点组肾小管上皮细胞线粒体ROS含量在体外降低约1.66倍,体内血清肌酐(Scr)和尿素氮(BUN)水平分别降低1.5和1.2 mmol/L。机制研究表明,纳米系统通过干扰NF-κB和Nrf2通路抑制炎症反应。本研究为AKI治疗提供了一种高效、低毒的策略。
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引用次数: 0
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