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Paradoxical Roles of Carbon Nanotubes in Cancer Therapy and Carcinogenesis 碳纳米管在癌症治疗和致癌过程中的矛盾作用
Pub Date : 2024-07-08 DOI: 10.3390/jnt5030006
Bohan Xu, Shunjie Wu, Yiyang Wang, Yuhe Ji, Shufeng Liang, Chunyan Wang, Xin Tian
Carbon nanotubes (CNTs), members of the nanomaterial family, are increasingly being used in consumer products and extensively studied for various biomedical applications. Due to their benign elemental composition, large surface area, and chemical and biological activities, CNTs demonstrate great potential in cancer therapy, including drug delivery, imaging analysis, photothermal therapy, photodynamic therapy, and radiotherapy. However, there is still a major knowledge gap when it comes to transitioning from research to clinical applications. One of the important issues is that the biological toxicity of CNTs, especially in terms of carcinogenesis, and the underlying mechanisms are not fully understood. Therefore, a thorough evaluation of toxicity and the underlying mechanisms of carcinogenesis is essential to enable the wide application of CNTs. In this review, we summarize the recent progress of CNTs as multifunctional therapeutics in cancer therapy. Furthermore, a detailed discussion is provided on the carcinogenesis and potential mechanisms of CNTs. Finally, the review ends with further challenges and prospects for CNTs with the expectation of facilitating their broader utilization.
碳纳米管(CNTs)是纳米材料家族的成员,正越来越多地应用于消费品中,并在各种生物医学应用中得到广泛研究。由于其良性元素组成、大表面积以及化学和生物活性,碳纳米管在癌症治疗方面具有巨大潜力,包括药物输送、成像分析、光热治疗、光动力治疗和放射治疗。然而,在从研究过渡到临床应用方面仍存在很大的知识差距。其中一个重要问题是,人们对碳纳米管的生物毒性(尤其是致癌方面)及其内在机制还不完全了解。因此,彻底评估毒性和致癌的基本机制对于实现 CNT 的广泛应用至关重要。在这篇综述中,我们总结了 CNTs 作为多功能疗法在癌症治疗方面的最新进展。此外,还详细讨论了 CNTs 的致癌作用和潜在机制。最后,综述以 CNTs 面临的进一步挑战和前景作为结尾,希望能促进 CNTs 的更广泛应用。
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引用次数: 0
Graphene Oxide Chemical Refining Screening to Improve Blood Compatibility of Graphene-Based Nanomaterials 通过氧化石墨烯化学提纯筛选改善石墨烯基纳米材料的血液相容性
Pub Date : 2024-02-20 DOI: 10.3390/jnt5010002
Fabio Pieretti, Alessandro Moretto, Emanuele Papini, R. Tavano
Graphene oxide (GO) nanoparticles, due to their favorable water solubility, compared to graphene (GA), are a hot research topic in biomedical and pharmaceutical research. However, GO clinical translation may be complicated by its high surface/volume ratio enhancing the interaction with human blood components. In fact, GO’s bi-dimensional nature and strong negative charge may lead to severe biological effects, such as thrombogenicity and immune cell activation. This study explores the impact of further GO surface chemical modulation on major adverse effects: blood plasma coagulation and hemolysis. To this aim, we refined GO nanoparticles by fine-tuned reduction chemistry, esterification and introduction of negative or positive charges. With this approach, we were able to mitigate plasma coagulation and hemolysis at variable degrees and to identify GO derivatives with improved biocompatibility. This opens the door to the progress of graphene-based nanotheranostic applications.
与石墨烯(GA)相比,氧化石墨烯(GO)纳米粒子具有良好的水溶性,是生物医学和制药研究领域的热门研究课题。然而,GO 的高表面/体积比会增强与人体血液成分的相互作用,这可能会使其临床转化变得复杂。事实上,GO 的二维性质和强负电荷可能会导致严重的生物效应,如血栓形成和免疫细胞激活。本研究探讨了进一步调节 GO 表面化学性质对血浆凝固和溶血等主要不良反应的影响。为此,我们通过微调还原化学、酯化和引入负电荷或正电荷来改进 GO 纳米粒子。通过这种方法,我们能够在不同程度上缓解血浆凝固和溶血,并确定了具有更好生物相容性的 GO 衍生物。这为基于石墨烯的纳米otheranostic应用的发展打开了大门。
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引用次数: 0
The Role of Fullerenes in Neurodegenerative Disorders 富勒烯在神经退行性疾病中的作用
Pub Date : 2024-01-16 DOI: 10.3390/jnt5010001
Daisy L. Wilson, J. Ahlawat, Mahesh Narayan
The use of carbon nanomaterials including fullerenes, carbon nanotubes, carbon nano-onions, carbon dots and carbon quantum dots for environmental applications has increased substantially. These nanoparticles are now used in the development of sensors and switches, in agriculture as smart fertilizers and in the biomedical realm for cancer therapy intervention, as antioxidants, in gene delivery and as theranostics. Here, we review the role of fullerenes as neuroprotectants. Their sp2 hybridized architectures and ability to intervene in the soluble-to-toxic transformation of amyloidogenic trajectories is highlighted here, along with other physico–chemical properties that impact interventional efficacy. Also highlighted are drawbacks that need to be overcome and future prospects.
碳纳米材料(包括富勒烯、碳纳米管、碳纳米离子、碳点和碳量子点)在环境领域的应用大幅增加。目前,这些纳米粒子已被用于开发传感器和开关,在农业领域用作智能肥料,在生物医学领域用于癌症治疗干预、抗氧化剂、基因递送和治疗。在此,我们回顾了富勒烯作为神经保护剂的作用。本文重点介绍了富勒烯的 sp2 杂化结构和干预淀粉样蛋白生成轨迹从可溶到毒性转化的能力,以及影响干预效果的其他物理化学特性。此外,还重点介绍了需要克服的缺点和未来前景。
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引用次数: 0
Efficacy of 15 nm Gold Nanoparticles for Image-Guided Gliosarcoma Radiotherapy 15纳米金纳米颗粒在图像引导胶质肉瘤放疗中的疗效
Pub Date : 2023-10-26 DOI: 10.3390/jnt4040021
Elette Engels, Michael Lerch, Stéphanie Corde, Moeava Tehei
Targeted brain cancer treatments are sorely needed to improve long-term prognosis, particularly for gliosarcoma and glioblastoma patients. Gold nanoparticles (GNPs) have unique properties including high atomic number, biocompatibility, and small size for cancer cell internalization. GNPs are consequently an ideal candidate for improved cancer targeting using image-guided radiotherapy. This work investigated 15 nm AuroVistTM GNPs for image-guided gliosarcoma radiotherapy and identified optimum GNP concentrations. The GNPs were found to be 15–20 nm using optical surface plasmon resonance absorption, with a (41.3 ± 0.3) nm hydrodynamic diameter. Confocal imaging showed that 50–500 µg/mL of the GNPs was well-internalized into the 9L cells within 24–48 h. γ-H2AX assays showed that 50–500 µg/mL of the GNPs radiosensitized the 9L cells irradiated with 125 and 150 kVp X-rays. However, only 500 µg/mL of the GNPs produced significant long-term dose enhancement with 150 kVp X-rays (with a sensitization enhancement ratio at 10% survival of 1.43, and 1.13 with 50 µg/mL) using clonogenic assay. CT imaging of the GNPs in the 9L tumors in Fischer rats further showed that GNP concentrations above 500 µg/mL were required to distinguish the tumor from the brain, and the GNPs were detected 48 h after injection. These promising results indicate that the GNPs can be used for selective gliosarcoma treatment with image-guided X-ray radiotherapy at concentrations above 500 µg/mL.
有针对性的脑癌治疗是改善长期预后的迫切需要,特别是对于胶质肉瘤和胶质母细胞瘤患者。金纳米粒子(GNPs)具有原子序数高、生物相容性好、体积小等特点,适合癌细胞内化。因此,GNPs是使用图像引导放射治疗改进癌症靶向的理想候选者。本研究研究了15 nm AuroVistTM用于图像引导胶质肉瘤放疗的GNPs,并确定了最佳GNP浓度。通过光学表面等离子体共振吸收,发现GNPs在15 ~ 20 nm之间,流体力学直径为(41.3±0.3)nm。共聚焦成像显示,在24-48 h内,50-500µg/mL的GNPs被很好地内化到9L细胞中。γ-H2AX实验显示,在125和150 kVp x射线照射下,50-500µg/mL的GNPs对9L细胞有放射致敏作用。然而,通过克隆测定,只有500µg/mL的GNPs在150 kVp x射线下产生显著的长期剂量增强(10%存活率时敏化增强比为1.43,50µg/mL时敏化增强比为1.13)。Fischer大鼠9L肿瘤中GNPs的CT成像进一步显示,GNP浓度大于500µg/mL才能区分肿瘤和脑,并在注射后48 h检测GNPs。这些有希望的结果表明,GNPs可用于图像引导x射线放射治疗选择性胶质肉瘤,浓度高于500µg/mL。
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引用次数: 0
Enhancing Antibody Exposure in the Central Nervous System: Mechanisms of Uptake, Clearance, and Strategies for Improved Brain Delivery 增强抗体在中枢神经系统中的暴露:摄取、清除的机制,以及改善大脑递送的策略
Pub Date : 2023-10-02 DOI: 10.3390/jnt4040020
Kelly Schwinghamer, Teruna J. Siahaan
Antibodies (mAbs) are attractive molecules for their application as a diagnostic and therapeutic agent for diseases of the central nervous system (CNS). mAbs can be generated to have high affinity and specificity to target molecules in the CNS. Unfortunately, only a very small number of mAbs have been specifically developed and approved for neurological indications. This is primarily attributed to their low exposure within the CNS, hindering their ability to reach and effectively engage their potential targets in the brain. This review discusses aspects of various barriers such as the blood–brain barrier (BBB) and blood–cerebrospinal fluid (CSF) barrier (BCSFB) that regulate the entry and clearance of mAbs into and from the brain. The roles of the glymphatic system on brain exposure and clearance are being described. We also discuss the proposed mechanisms of the uptake of mAbs into the brain and for clearance. Finally, several methods of enhancing the exposure of mAbs in the CNS were discussed, including receptor-mediated transcytosis, osmotic BBB opening, focused ultrasound (FUS), BBB-modulating peptides, and enhancement of mAb brain retention.
抗体(mab)作为中枢神经系统(CNS)疾病的诊断和治疗药物,具有广泛的应用前景。生成的单克隆抗体对中枢神经系统中的靶分子具有高亲和力和特异性。不幸的是,只有极少数单克隆抗体被专门开发并批准用于神经适应症。这主要归因于它们在中枢神经系统内的低暴露,阻碍了它们到达并有效地参与大脑中潜在目标的能力。本文讨论了各种屏障,如血脑屏障(BBB)和血脑脊液屏障(BCSFB),它们调节单克隆抗体进入和清除大脑。描述了淋巴系统在脑暴露和清除中的作用。我们还讨论了单克隆抗体进入大脑和清除的机制。最后,讨论了几种增强单抗在中枢神经系统暴露的方法,包括受体介导的胞饮作用、渗透血脑屏障打开、聚焦超声(FUS)、血脑屏障调节肽和增强单抗脑保留。
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引用次数: 0
Recent Advances in Combating Bacterial Infections by Using Hybrid Nano-Systems 利用混合纳米系统对抗细菌感染的最新进展
Pub Date : 2023-09-08 DOI: 10.3390/jnt4030019
Unnati Patel, Emily C. Hunt
In recent years, antimicrobial resistance in many human pathogens has become a serious health concern. Since infections with resistant pathogens cannot be treated with traditional antimicrobial drugs, new strategies are necessary to fight bacterial infections. Hybrid nano-systems may provide a solution to this problem, by combining multiple mechanisms for killing bacteria to synergistically increase the effectiveness of the antimicrobial treatment. In this review, we highlight recent advances in the development of hybrid nano-systems for the treatment of bacterial infections. We discuss the use of hybrid nano-systems for combinational therapy, focusing on various triggering mechanisms for drug release and the development of biomimetic nanomaterials. We also examine inherently antimicrobial nano-systems and their uses in preventing infections due to wounds and medical implants. This review summarizes recent advances and provides insight into the future development of antimicrobial treatments using hybrid nanomaterials.
近年来,许多人类病原体的抗微生物耐药性已成为一个严重的健康问题。由于耐药病原体的感染不能用传统的抗菌药物治疗,因此有必要采取新的策略来对抗细菌感染。混合纳米系统可以通过结合多种杀菌机制来协同提高抗菌治疗的有效性,从而为这个问题提供解决方案。在这篇综述中,我们重点介绍了用于治疗细菌感染的混合纳米系统的最新进展。我们讨论了混合纳米系统用于联合治疗,重点讨论了药物释放的各种触发机制和仿生纳米材料的开发。我们还研究了固有的抗菌纳米系统及其在预防伤口和医疗植入物感染方面的应用。这篇综述总结了最近的进展,并对使用混合纳米材料的抗菌治疗的未来发展提供了见解。
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引用次数: 2
Aptamers as Theranostics in Cardiovascular Diseases 适体作为心血管疾病的Theranos
Pub Date : 2023-09-06 DOI: 10.3390/jnt4030018
Manish Ramchandani, Priyanka Kumari, Amit Goyal
Cardiovascular disease (particularly atherosclerosis) is a leading cause of death around the world, and there still exists a need for improved diagnostic techniques and treatments to improve patient outcomes as well as minimize the disease’s global burden. Aptamers are short, single-stranded DNA or RNA molecules that are accompanied by unique characteristics such as specificity, high binding affinity, ease of cellular internalization, and rapid tissue accumulation capabilities, offering great potential as theranostic agents in cardiovascular diseases with significantly improved sensitivity and accuracy. These theranostic agents provide a combination of therapy and diagnostics in which aptamers may diagnose and treat disease simultaneously. Therefore, this review article summarizes the role of aptamer-based probes for imaging and theranostics in cardiovascular disease. It also provides insight into current research and future treatment techniques that are very relevant for future clinical practice with the aim of improving the quality of life of cardiovascular disease patients.
心血管疾病(尤其是动脉粥样硬化)是世界各地死亡的主要原因,仍然需要改进诊断技术和治疗,以改善患者的预后,并将疾病的全球负担降至最低。适体是短的单链DNA或RNA分子,具有独特的特性,如特异性、高结合亲和力、易于细胞内化和快速组织积累能力,在心血管疾病中具有巨大的治疗潜力,其敏感性和准确性显著提高。这些治疗剂提供了治疗和诊断的组合,其中适体可以同时诊断和治疗疾病。因此,本文综述了基于适体的探针在心血管疾病成像和治疗中的作用。它还提供了对当前研究和未来治疗技术的见解,这些技术与未来的临床实践非常相关,目的是提高心血管疾病患者的生活质量。
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引用次数: 0
Nanotheranostics: Platforms, Current Applications, and Mechanisms of Targeting in Breast and Prostate Cancers 纳米技术:乳腺癌和前列腺癌靶向的平台、当前应用和机制
Pub Date : 2023-08-10 DOI: 10.3390/jnt4030016
P. Akpa, I. E. Peter, A. M. Onwuka, B. Obi, M. Akunne, C. Nworu, P. Ejikeme, T. Akunne, A. Attama, P. Akah
Globally, cancer is one of the deadliest diseases, needing a meticulous diagnosis and targeted treatment plan to achieve an initial prognosis, followed by precision and optimization in treatment. Nonselective targeting, difficulty in accurately monitoring treatment end-results, serious drug side-effects, and severity of disease resulting in metastasis are the key flaws of traditional techniques. Nanotechnology and nanoparticles possess special features to completely transform the field of diagnosis and treatment of cancer. A holistic strategy that employs a dual function of diagnosis and therapy while utilizing a nanocarrier is referred to as a nanotheranostic. The nanotheranostic framework was created to surmount a variety of biological and physiological obstacles, effectively delivering the cargo to the intended target location, while simultaneously facilitating therapeutic intervention, surveillance, and validation to demonstrate improved treatment effectiveness. As a result, a nanotheranostic platform can be useful for targeted drug delivery, release, and distribution assessment, in addition to patient classification and survival. Nanotheranostic techniques also lead to reduced drug side-effects compared with conventional therapies. In this review, we outline current studies on nanotheranostics and their advantages over conventional treatment strategies, the applications and challenges/limitations of nanotheranostics, and the mechanisms of targeting in breast and prostate cancers.
在全球范围内,癌症是最致命的疾病之一,需要精心诊断和有针对性的治疗计划来实现初步预后,然后进行精确和优化的治疗。非选择性靶向、难以准确监测治疗最终结果、严重的药物副作用以及导致转移的疾病严重程度是传统技术的关键缺陷。纳米技术和纳米颗粒具有完全改变癌症诊断和治疗领域的特殊特征。在利用纳米载体的同时采用诊断和治疗双重功能的整体策略被称为纳米治疗。创建纳米治疗框架是为了克服各种生物和生理障碍,有效地将货物运送到预期的目标位置,同时促进治疗干预、监测和验证,以证明治疗效果的提高。因此,除了患者分类和存活率外,纳米治疗平台还可用于靶向药物递送、释放和分布评估。与传统疗法相比,纳米技术还可以减少药物副作用。在这篇综述中,我们概述了目前对纳米治疗药物的研究及其相对于传统治疗策略的优势,纳米治疗药物在乳腺癌和前列腺癌中的应用和挑战/局限性,以及靶向机制。
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引用次数: 0
Smart Platinum Nanostructures: A Journey from Synthesis to Advanced Theranostic Applications 智能铂纳米结构:从合成到高级Theranos应用的历程
Pub Date : 2023-08-10 DOI: 10.3390/jnt4030017
Akash Kumar, Nabojit Das, R. Rayavarapu
A significant paradigm shift has been observed in the past decade in the area of theranostics owing to the development of various isotropic and anisotropic metal nanostructures, simultaneous with improved imaging modalities. Platinum-based nanostructures are advancing in a plethora of clinical applications as theranostics tools owing to their unique behavior concerning their size, shape, and surface chemistry at the nanoscale regime. Platinum nanostructures are optically active and provide significant potential to the field of theranostics by simplifying diagnosis and therapeutics, thus providing key solutions through nano-enabled technologies. The review emphasizes the potential of platinum nanostructures that have immense potential in vitro and in vivo scenarios as nanocarriers. Still, their potential in terms of photothermal active agents has not been well explored or reported. Nanotheranostics has emerged as a platform where various noble metal nanoparticles are effectively efficient as photothermal agents in bringing precision to therapy and diagnostics. Platinum, as an antioxidant and a stable nanocarrier, will enable them to act as photosensitizers when conjugated to affinity molecules and plays a key role in efficient treatment and diagnosis. The review envisions bringing together the possibilities of the safe-by-design synthesis of platinum nanostructures and their potential role in both in vitro and in vivo applications. A roadmap describing the challenges, pitfalls, and possibilities of influencing platinum nanostructures to overcome the existing biological/targeting barriers is elaborated. This review provides a literature survey on platinum nanostructures in theranostics, providing novel strategies in bio-imaging, diagnostics, and nanomedicine.
在过去的十年里,由于各种各向同性和各向异性金属纳米结构的发展,以及成像模式的改进,在治疗学领域观察到了重大的范式转变。铂基纳米结构作为治疗工具,由于其在纳米尺度范围内的尺寸、形状和表面化学方面的独特行为,在大量临床应用中取得了进展。铂纳米结构具有光学活性,通过简化诊断和治疗,为治疗学领域提供了巨大潜力,从而通过纳米技术提供了关键解决方案。该综述强调了铂纳米结构作为纳米载体在体外和体内具有巨大潜力的潜力。然而,它们在光热活性剂方面的潜力尚未得到很好的探索或报道。纳米技术已经成为一个平台,在这个平台上,各种贵金属纳米颗粒作为光热剂有效地为治疗和诊断带来精确性。铂作为一种抗氧化剂和稳定的纳米载体,当与亲和分子结合时,将使它们能够充当光敏剂,并在有效的治疗和诊断中发挥关键作用。该综述设想通过设计安全合成铂纳米结构的可能性及其在体外和体内应用中的潜在作用。阐述了影响铂纳米结构克服现有生物/靶向障碍的挑战、陷阱和可能性的路线图。这篇综述提供了一篇关于治疗学中铂纳米结构的文献综述,为生物成像、诊断和纳米医学提供了新的策略。
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引用次数: 0
An Overview of Nanotherapeutic Drug Delivery Options for the Management of Glioblastoma 胶质母细胞瘤管理的纳米治疗药物递送选择综述
Pub Date : 2023-08-01 DOI: 10.3390/jnt4030015
W. H. Pentz, Vincenzo J. Pizzuti, Matthew E. Halbert, Tritan J. Plute, P. Lockman, S. Sprowls
Glioblastoma is the most common primary, malignant brain tumor that remains uniformly lethal in nearly all cases as a result of extreme cellular heterogeneity, treatment resistance, and recurrence. A major hurdle in therapeutic delivery to brain tumors is the blood–brain barrier (BBB), which is the tightly regulated vascular barrier between the brain parenchyma and systemic circulation that prevents distribution of otherwise beneficial chemotherapeutics to central nervous system tumors. To overcome the obstacle of drug delivery beyond the BBB, nanoparticle formulations have come to the forefront, having demonstrated success in preclinical observations, but have not translated well into the clinical setting. In summary, this review article discusses brain tumors and challenges for drug delivery caused by the BBB, explores the benefits of nanoparticle formulations for brain tumor delivery, describes the characteristics these formulations possess that make them attractive therapeutic strategies, and provides preclinical examples that implement nanoparticles within glioma treatment regimens. Additionally, we explore the pitfalls associated with clinical translation and conclude with remarks geared toward overcoming these issues.
胶质母细胞瘤是最常见的原发性恶性脑肿瘤,由于其极端的细胞异质性、治疗耐药性和复发,几乎在所有病例中都是致命的。对脑肿瘤进行治疗的主要障碍是血脑屏障(BBB),这是脑实质和体循环之间严格调节的血管屏障,阻止了原本有益的化疗药物向中枢神经系统肿瘤的分布。为了克服血脑屏障之外的药物传递障碍,纳米颗粒制剂已经走到了前沿,在临床前观察中取得了成功,但尚未很好地转化为临床环境。总之,这篇综述文章讨论了脑屏障引起的脑肿瘤和药物递送的挑战,探讨了纳米颗粒配方对脑肿瘤递送的好处,描述了这些配方所具有的使其具有吸引力的治疗策略的特征,并提供了在胶质瘤治疗方案中实施纳米颗粒的临床前示例。此外,我们探讨了与临床翻译相关的陷阱,并总结了针对克服这些问题的评论。
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引用次数: 0
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