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Surface Adsorption of the Alpha-Emitter Astatine-211 to Gold Nanoparticles Is Stable In Vivo and Potentially Useful in Radionuclide Therapy α发射体Astatine-211对金纳米粒子的表面吸附在体内是稳定的,并有可能用于放射性核素治疗
Pub Date : 2021-10-01 DOI: 10.3390/jnt2040012
Emanuel Sporer, C. Poulie, S. Lindegren, Emma Aneheim, H. Jensen, T. Bäck, P. Kempen, A. Kjaer, M. Herth, A. I. Jensen
Targeted α-therapy (TAT) can eradicate tumor metastases while limiting overall toxicity. One of the most promising α-particle emitters is astatine-211 (211At). However, 211At-carbon bonds are notoriously unstable in vivo and no chelators are available. This hampers its adoption in TAT. In this study, the stability of 211At on the surface of gold nanoparticles (AuNPs) was investigated. The employed AuNPs had sizes in the 25–50 nm range. Radiolabeling by non-specific surface-adsorption in >99% radiochemical yield was achieved by mixing 211At and AuNPs both before and after polyethylene glycol (PEG) coating. The resulting 211At-AuNPs were first challenged by harsh oxidation with sodium hypochlorite, removing roughly 50% of the attached 211At. Second, incubation in mouse serum followed by a customized stability test, showed a stability of >95% after 4 h in serum. This high stability was further confirmed in an in vivo study, with comparison to a control group of free 211At. The AuNP-associated 211At showed low uptake in stomach and thyroid, which are hallmark organs of uptake of free 211At, combined with long circulation and high liver and spleen uptake, consistent with nanoparticle biodistribution. These results support that gold surface-adsorbed 211At has high biological stability and is a potentially useful delivery system in TAT.
靶向α-治疗(TAT)可以根除肿瘤转移,同时限制总体毒性。最有前途的α粒子发射体之一是astatine-211(211At)。然而,211At碳键在体内是出了名的不稳定,并且没有可用的螯合剂。这阻碍了它在TAT中的采用。在本研究中,研究了211At在金纳米颗粒(AuNPs)表面的稳定性。所使用的AuNPs的尺寸在25–50 nm范围内。通过在聚乙二醇(PEG)涂层前后混合211At和AuNP,以>99%的放射化学产率通过非特异性表面吸附进行放射标记。所得的211At-AuNP首先通过用次氯酸钠的剧烈氧化来挑战,去除大约50%的附着的211At。其次,在小鼠血清中孵育,然后进行定制的稳定性测试,在血清中4小时后显示出>95%的稳定性。与游离211At的对照组相比,这种高稳定性在体内研究中得到了进一步证实。AuNP相关的211At在胃和甲状腺中显示出低摄取,这是摄取游离211At的标志性器官,结合长循环和高肝脏和脾脏摄取,与纳米颗粒的生物分布一致。这些结果支持金表面吸附211At具有高的生物稳定性,并且是TAT中潜在有用的递送系统。
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引用次数: 4
Dissecting the Inorganic Nanoparticle-Driven Interferences on Adhesome Dynamics 无机纳米粒子驱动的对成体动力学的干扰
Pub Date : 2021-09-02 DOI: 10.3390/jnt2030011
Vladimir Mulens-Arias
Inorganic nanoparticles have emerged as an attractive theranostic tool applied to different pathologies such as cancer. However, the increment in inorganic nanoparticle application in biomedicine has prompted the scientific community to assess their potential toxicities, often preventing them from entering clinical settings. Cytoskeleton network and the related adhesomes nest are present in most cellular processes such as proliferation, migration, and cell death. The nanoparticle treatment can interfere with the cytoskeleton and adhesome dynamics, thus inflicting cellular damage. Therefore, it is crucial dissecting the molecular mechanisms involved in nanoparticle cytotoxicity. This review will briefly address the main characteristics of different adhesion structures and focus on the most relevant effects of inorganic nanoparticles with biomedical potential on cellular adhesome dynamics. Besides, the review put into perspective the use of inorganic nanoparticles for cytoskeleton targeting or study as a versatile tool. The dissection of the molecular mechanisms involved in the nanoparticle-driven interference of adhesome dynamics will facilitate the future development of nanotheranostics targeting cytoskeleton and adhesomes to tackle several diseases, such as cancer.
无机纳米颗粒已经成为一种有吸引力的治疗工具,应用于不同的病理学,如癌症。然而,无机纳米颗粒在生物医学中应用的增加促使科学界评估其潜在毒性,通常阻止其进入临床环境。细胞骨架网络和相关的粘附体巢存在于大多数细胞过程中,如增殖、迁移和细胞死亡。纳米颗粒处理可以干扰细胞骨架和粘附动力学,从而造成细胞损伤。因此,剖析纳米颗粒细胞毒性的分子机制至关重要。这篇综述将简要介绍不同粘附结构的主要特征,并重点介绍具有生物医学潜力的无机纳米颗粒对细胞粘附动力学的最相关影响。此外,该综述展望了无机纳米颗粒作为一种多功能工具用于细胞骨架靶向或研究的前景。对纳米颗粒驱动的粘附体动力学干扰所涉及的分子机制的剖析将促进靶向细胞骨架和粘附体的纳米治疗学的未来发展,以解决多种疾病,如癌症。
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引用次数: 1
Theranostic Applications of Nanoparticle-Mediated Photoactivated Therapies 纳米粒子介导的光激活疗法的治疗应用
Pub Date : 2021-08-03 DOI: 10.3390/jnt2030009
Shalini Sharma, A. Zvyagin, I. Roy
Nanoparticle-mediated light-activated therapies, such as photodynamic therapy and photothermal therapy, are earnestly being viewed as efficient interventional strategies against several cancer types. Theranostics is a key hallmark of cancer nanomedicine since it allows diagnosis and therapy of both primary and metastatic cancer using a single nanoprobe. Advanced in vivo diagnostic imaging using theranostic nanoparticles not only provides precise information about the location of tumor/s but also outlines the narrow time window corresponding to the maximum tumor-specific drug accumulation. Such information plays a critical role in guiding light-activated therapies with high spatio-temporal accuracy. Furthermore, theranostics facilitates monitoring the progression of therapy in real time. Herein, we provide a general review of the application of theranostic nanoparticles for in vivo image-guided light-activated therapy in cancer. The imaging modalities considered here include fluorescence imaging, photoacoustic imaging, thermal imaging, magnetic resonance imaging, X-ray computed tomography, positron emission tomography, and single-photon emission computed tomography. The review concludes with a brief discussion about the broad scope of theranostic light-activated nanomedicine.
纳米粒子介导的光激活疗法,如光动力疗法和光热疗法,正被认真地视为对抗几种癌症类型的有效介入策略。治疗学是癌症纳米医学的一个关键标志,因为它允许使用单个纳米探针诊断和治疗原发性和转移性癌症。使用治疗性纳米颗粒的先进体内诊断成像不仅提供了关于肿瘤位置的精确信息,而且还概述了与肿瘤特异性药物最大积累相对应的狭窄时间窗口。这些信息在指导具有高时空准确性的光激活疗法中起着关键作用。此外,治疗学有助于实时监测治疗的进展。在此,我们提供了治疗纳米颗粒在体内图像引导光激活治疗癌症的应用综述。这里考虑的成像方式包括荧光成像、光声成像、热成像、磁共振成像、x射线计算机断层扫描、正电子发射断层扫描和单光子发射计算机断层扫描。本文最后简要讨论了光激活治疗纳米药物的广泛应用范围。
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引用次数: 5
Nanoscale Carbon-Polymer Dots for Theranostics and Biomedical Exploration 纳米尺度碳聚合物点用于治疗和生物医学探索
Pub Date : 2021-07-29 DOI: 10.3390/jnt2030008
S. Sharker, Minjae Do
In recent years, new carbonized nanomaterials have emerged in imaging, sensing, and various biomedical applications. Published literature shows that carbon dots (CDs) have been explored more extensively than any other nanomaterials. However, its polymeric version, carbon polymer dots (CPDs), did not get much attention. The non-conjugated and single-particle CPDs have all the merits of polymer and CDs, such as photoluminescent properties. The partially carbonized CPDs can be applied like CDs without surface passivation and functionalization. This merit can be further enhanced through the selection of desired precursors and control of carbonization synthesis. CPDs can absorb UV-visible-NIR light and can enhance the photoresponsive chemical and biochemical interactions. This review aims to introduce this area of renewed interest and provide insights into current developments of CPDs nanoparticles and present an overview of chemical, biological, and therapeutic applications.
近年来,新型碳化纳米材料在成像、传感和各种生物医学领域得到了广泛的应用。已发表的文献表明,碳点(cd)比任何其他纳米材料都得到了更广泛的探索。然而,它的聚合物版本,碳聚合物点(CPDs),并没有得到太多的关注。非共轭和单粒子CPDs具有聚合物和cd的所有优点,如光致发光性能。部分碳化的cpd可以像cd一样使用,不需要表面钝化和功能化。通过对前驱体的选择和炭化合成的控制,可以进一步提高这一优点。CPDs可以吸收紫外-可见-近红外光,增强光响应性化学和生化相互作用。这篇综述旨在介绍这一领域的新兴趣,并提供当前发展的见解,CPDs纳米颗粒,并提出了化学,生物和治疗应用的概述。
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引用次数: 8
Improvements in Gold Nanorod Biocompatibility with Sodium Dodecyl Sulfate Stabilization 十二烷基硫酸钠稳定金纳米棒生物相容性的改进
Pub Date : 2021-07-16 DOI: 10.3390/jnt2030010
Rossana Terracciano, A. Zhang, Mathieu L. Simeral, D. Demarchi, J. Hafner, Carly S. Filgueira
Due to their well-defined plasmonic properties, gold nanorods (GNRs) can be fabricated with optimal light absorption in the near-infrared region of the electromagnetic spectrum, which make them suitable for cancer-related theranostic applications. However, their controversial safety profile, as a result of surfactant stabilization during synthesis, limits their clinical translation. We report a facile method to improve GNR biocompatibility through the presence of sodium dodecyl sulfate (SDS). GNRs (120 × 40 nm) were synthesized through a seed-mediated approach, using cetyltrimethylammonium bromide (CTAB) as a cationic surfactant to direct the growth of nanorods and stabilize the particles. Post-synthesis, SDS was used as an exchange ligand to modify the net surface charge of the particles from positive to negative while maintaining rod stability in an aqueous environment. GNR cytotoxic effects, as well as the mechanisms of their cellular uptake, were examined in two different cancer cell lines, Lewis lung carcinoma (LLC) and HeLa cells. We not only found a significant dose-dependent effect of GNR treatment on cell viability but also a time-dependent effect of GNR surfactant charge on cytotoxicity over the two cell lines. Our results promote a better understanding of how we can mediate the undesired consequences of GNR synthesis byproducts when exposed to a living organism, which so far has limited GNR use in cancer theranostics.
由于其明确的等离子体性质,金纳米棒(GNR)可以在电磁光谱的近红外区域制造出最佳的光吸收,这使其适用于癌症相关的治疗应用。然而,由于表面活性剂在合成过程中的稳定性,它们有争议的安全性限制了它们的临床应用。我们报道了一种通过十二烷基硫酸钠(SDS)存在来改善GNR生物相容性的简单方法。以十六烷基三甲基溴化铵(CTAB)为阳离子表面活性剂,通过种子介导的方法合成了GNRs(120×40nm),以引导纳米棒的生长并稳定颗粒。合成后,使用SDS作为交换配体,将颗粒的净表面电荷从正改性为负,同时在水性环境中保持棒的稳定性。在两种不同的癌症细胞系Lewis肺癌(LLC)和HeLa细胞中检测了GNR的细胞毒性效应及其细胞摄取机制。我们不仅发现GNR处理对细胞活力的显著剂量依赖性影响,而且发现GNR表面活性剂电荷对两种细胞系的细胞毒性的时间依赖性影响。我们的研究结果有助于更好地理解我们如何在暴露于活体时介导GNR合成副产物的不良后果,这迄今为止限制了GNR在癌症治疗中的应用。
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引用次数: 5
Deciphering Exhaled Aerosol Fingerprints for Early Diagnosis and Personalized Therapeutics of Obstructive Respiratory Diseases in Small Airways 解读呼气气溶胶指纹用于小型航空公司阻塞性呼吸道疾病的早期诊断和个性化治疗
Pub Date : 2021-06-22 DOI: 10.3390/jnt2030007
X. Si, J. Xi
Respiratory diseases often show no apparent symptoms at their early stages and are usually diagnosed when permanent damages have been made to the lungs. A major site of lung pathogenesis is the small airways, which make it highly challenging to detect using current techniques due to the diseases’ location (inaccessibility to biopsy) and size (below normal CT/MRI resolution). In this review, we present a new method for lung disease detection and treatment in small airways based on exhaled aerosols, whose patterns are uniquely related to the health of the lungs. Proof-of-concept studies are first presented in idealized lung geometries. We subsequently describe the recent developments in feature extraction and classification of the exhaled aerosol images to establish the relationship between the images and the underlying airway remodeling. Different feature extraction algorithms (aerosol density, fractal dimension, principal mode analysis, and dynamic mode decomposition) and machine learning approaches (support vector machine, random forest, and convolutional neural network) are elaborated upon. Finally, future studies and frequent questions related to clinical applications of the proposed aerosol breath testing are discussed from the authors’ perspective. The proposed breath testing has clinical advantages over conventional approaches, such as easy-to-perform, non-invasive, providing real-time feedback, and is promising in detecting symptomless lung diseases at early stages.
呼吸道疾病通常在早期没有明显症状,通常在肺部受到永久性损伤时才被诊断出来。肺部发病机制的一个主要部位是小气道,由于疾病的位置(无法进行活检)和大小(低于正常的CT/MRI分辨率),使用现有技术进行检测具有很大的挑战性。在这篇综述中,我们提出了一种基于呼出气溶胶的小气道肺部疾病检测和治疗新方法,其模式与肺部健康独特相关。概念验证研究首先出现在理想化的肺部几何形状中。随后,我们描述了呼出气溶胶图像的特征提取和分类的最新进展,以建立图像与潜在气道重塑之间的关系。阐述了不同的特征提取算法(气溶胶密度、分形维数、主模式分析和动态模式分解)和机器学习方法(支持向量机、随机森林和卷积神经网络)。最后,从作者的角度讨论了气溶胶呼吸测试的未来研究和临床应用中常见的问题。与传统方法相比,所提出的呼吸测试具有临床优势,如易于执行、无创、提供实时反馈,在早期检测无症状肺部疾病方面很有前景。
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引用次数: 4
Cellular Investigations on Mechanistic Biocompatibility of Green Synthesized Calcium Oxide Nanoparticles with Danio rerio 绿色合成氧化钙纳米颗粒与微生物相容性的细胞研究
Pub Date : 2021-03-09 DOI: 10.3390/JNT2010004
Rashke Eram, P. Kumari, P. Panda, Sonal Singh, B. Sarkar, M. Mallick, S. Verma
The utility of calcium oxide nanoparticles in the biomedical and physical fields has instigated their biocompatible synthesis and production. Moreover, it is important to investigate their biocompatibility at the molecular level for biomedical and ecotoxicological concern. This study explores the green synthesis of calcium oxide nanoparticles (CaONP) using Crescentia cujete leaf extract. The synthesized CaONP were found to have a size of 62 ± 06 nm and a hydrodynamic diameter of 246 ± 12 nm, as determined by FE-SEM and dynamic light scattering (DLS). CaONP was stable in fish medium with a zeta potential of −23 ± 11 mV. The biocompatibility of the CaONP was investigated with adult zebrafish bearing an LC50 of 86.32 µg/mL. Cellular and molecular investigation revealed the mechanism of biocompatibility as a consequence of elicited reactive oxygen species leading to apoptosis, due to accumulation and internalization of CaONP in exposed zebrafish. The study provided detailed information about the mechanistic biocompatibility and a defined horizon of green synthesis of CaONP for biomedical and ecological purposes.
氧化钙纳米颗粒在生物医学和物理领域的应用促进了其生物相容性的合成和生产。此外,在分子水平上研究它们的生物相容性对生物医学和生态毒理学具有重要意义。本研究探讨了利用月牙叶提取物绿色合成氧化钙纳米颗粒(CaONP)的方法。通过FE-SEM和动态光散射(DLS)测定,合成的CaONP的粒径为62±06 nm,水动力直径为246±12 nm。CaONP在鱼培养基中稳定,zeta电位为- 23±11 mV。CaONP与成年斑马鱼的生物相容性研究,LC50为86.32µg/mL。细胞和分子研究揭示了暴露的斑马鱼体内CaONP的积累和内化导致活性氧诱导细胞凋亡的生物相容性机制。该研究提供了CaONP在生物医学和生态方面的生物相容性机制和绿色合成前景的详细信息。
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引用次数: 17
An Assessment of InP/ZnS as Potential Anti-Cancer Therapy: Quantum Dot Treatment Increases Apoptosis in HeLa Cells InP/ZnS作为潜在抗癌疗法的评估:量子点治疗增加HeLa细胞的凋亡
Pub Date : 2021-01-20 DOI: 10.3390/JNT2010002
V. Davenport, Cullen Horstmann, Rishi B. Patel, Qi-Hui Wu, Kyoungtae Kim
InP/ZnS quantum dots (QDs) are an emerging option in QD technologies for uses of fluorescent imaging as well as targeted drug and anticancer therapies based on their customizable properties. In this study we explored effects of InP/ZnS when treated with HeLa cervical cancer cells. We employed XTT viability assays, reactive oxygen species (ROS) analysis, and apoptosis analysis to better understand cytotoxicity extents at different concentrations of InP/ZnS. In addition, we compared the transcriptome profile from the QD-treated HeLa cells with that of untreated HeLa cells to identify changes to the transcriptome in response to the QD. RT-qPCR assay was performed to confirm the findings of transcriptome analysis, and the QD mode of action was illustrated. Our study determined both IC50 concentration of 69 µg/mL and MIC concentration of 167 µg/mL of InP/ZnS. It was observed via XTT assay that cell viability was decreased significantly at the MIC. Production of superoxide, measured by ROS assay with flow cytometry, was decreased, whereas levels of nitrogen radicals increased. Using analysis of apoptosis, we found that induced cell death in the QD-treated samples was shown to be significantly increased when compared to untreated cells. We conclude InP/ZnS QD to decrease cell viability by inducing stress via ROS levels, apoptosis induction, and alteration of transcriptome.
InP/ZnS量子点(QDs)是QD技术中的一种新兴选择,用于荧光成像以及基于其可定制特性的靶向药物和抗癌治疗。在本研究中,我们探讨了InP/ZnS在HeLa宫颈癌症细胞治疗中的作用。我们采用XTT活力分析、活性氧(ROS)分析和细胞凋亡分析来更好地了解不同浓度InP/ZnS的细胞毒性程度。此外,我们比较了QD处理的HeLa细胞和未处理的HeLa细胞的转录组谱,以确定转录组对QD的反应变化。进行RT-qPCR测定以证实转录组分析的结果,并说明了QD的作用模式。我们的研究确定了InP/ZnS的IC50浓度为69µg/mL,MIC浓度为167µg/mL。通过XTT测定观察到细胞活力在MIC下显著降低。通过流式细胞术ROS测定,超氧化物的产生减少,而氮自由基的水平增加。通过对细胞凋亡的分析,我们发现QD处理的样品中诱导的细胞死亡与未处理的细胞相比显著增加。我们得出结论,InP/ZnS QD通过ROS水平、细胞凋亡诱导和转录组的改变诱导应激,从而降低细胞活力。
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引用次数: 7
Nanomaterial-Mediated Theranostics for Vascular Diseases 纳米材料介导的血管疾病治疗
Pub Date : 2020-12-22 DOI: 10.3390/jnt2010001
S. Agrawal, S. Nooti, Harbinder Singh, Vikrant Rai
Nanotechnology could offer a new complementary strategy for the treatment of vascular diseases including coronary, carotid, or peripheral arterial disease due to narrowing or blockage of the artery caused by atherosclerosis. These arterial diseases manifest correspondingly as angina and myocardial infarction, stroke, and intermittent claudication of leg muscles during exercise. The pathogenesis of atherosclerosis involves biological events at the cellular and molecular level, thus targeting these using nanomaterials precisely and effectively could result in a better outcome. Nanotechnology can mitigate the pathological events by enhancing the therapeutic efficacy of the therapeutic agent by delivering it at the point of a lesion in a controlled and efficacious manner. Further, combining therapeutics with imaging will enhance the theranostic ability in atherosclerosis. Additionally, nanoparticles can provide a range of delivery systems for genes, proteins, cells, and drugs, which individually or in combination can address various problems within the arteries. Imaging studies combined with nanoparticles helps in evaluating the disease progression as well as the response to the treatment because imaging and diagnostic agents can be delivered precisely to the targeted destinations via nanocarriers. This review focuses on the use of nanotechnology in theranostics of coronary artery and peripheral arterial disease.
纳米技术可以为治疗血管疾病提供一种新的补充策略,包括冠状动脉、颈动脉或外周动脉疾病,这些疾病是由动脉粥样硬化引起的动脉狭窄或堵塞引起的。这些动脉疾病相应地表现为心绞痛和心肌梗死、中风和运动时腿部肌肉间歇性跛行。动脉粥样硬化的发病机制涉及细胞和分子水平的生物事件,因此使用纳米材料精确有效地靶向这些生物事件可能会获得更好的结果。纳米技术可以通过以可控和有效的方式将治疗剂输送到病变点,从而增强治疗剂的治疗效果,从而减轻病理事件。此外,将治疗与影像学相结合将提高动脉粥样硬化的治疗能力。此外,纳米颗粒可以为基因、蛋白质、细胞和药物提供一系列的传递系统,它们单独或联合起来可以解决动脉内的各种问题。成像研究结合纳米颗粒有助于评估疾病进展以及对治疗的反应,因为成像和诊断试剂可以通过纳米载体精确地传递到目标目的地。本文综述了纳米技术在冠状动脉和外周动脉疾病治疗中的应用。
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引用次数: 3
Use of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) via Multiple Imaging Modalities and Modifications to Reduce Cytotoxicity: An Educational Review 使用超顺磁性氧化铁纳米颗粒(SPIONs)通过多种成像方式和修改,以减少细胞毒性:教育综述
Pub Date : 2020-12-09 DOI: 10.3390/jnt1010008
Nicholas R. Nelson, J. Port, M. Pandey
The aim of the present educational review on superparamagnetic iron oxide nanoparticles (SPIONs) is to inform and guide young scientists and students about the potential use and challenges associated with SPIONs. The present review discusses the basic concepts of magnetic resonance imaging (MRI), basic construct of SPIONs, cytotoxic challenges associated with SPIONs, shape and sizes of SPIONs, site-specific accumulation of SPIONs, various methodologies applied to reduce cytotoxicity including coatings with various materials, and application of SPIONs in targeted delivery of chemotherapeutics (Doxorubicin), biotherapeutics (DNA, siRNA), and positron emission tomography (PET) imaging applications.
超顺磁性氧化铁纳米颗粒(SPIONs)的教育综述的目的是告知和指导青年科学家和学生关于SPIONs的潜在用途和相关的挑战。本文综述了磁共振成像(MRI)的基本概念、SPIONs的基本结构、与SPIONs相关的细胞毒性挑战、SPIONs的形状和大小、SPIONs的位点特异性积累、用于降低细胞毒性的各种方法,包括不同材料的涂层、SPIONs在化疗药物(阿霉素)、生物治疗药物(DNA、siRNA)和正电子发射层析成像(PET)成像中的应用。
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引用次数: 34
期刊
Journal of nanotheranostics
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