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Critical parameters to translate gold nanoparticles as radiosensitizing agents into the clinic. 将金纳米颗粒转化为放射增敏剂进入临床的关键参数。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-11-01 Epub Date: 2023-03-29 DOI: 10.1002/wnan.1886
Kave Moloudi, Ali Khani, Masoud Najafi, Rasool Azmoonfar, Mehdi Azizi, Houra Nekounam, Mahsa Sobhani, Sophie Laurent, Hadi Samadian

Radiotherapy is an inevitable choice for cancer treatment that is applied as combinatorial therapy along with surgery and chemotherapy. Nevertheless, radiotherapy at high doses kills normal and tumor cells at the same time. In addition, some tumor cells are resistant to radiotherapy. Recently, many researchers have focused on high-Z nanomaterials as radiosensitizers for radiotherapy. Among them, gold nanoparticles (GNPs) have shown remarkable potential due to their promising physical, chemical, and biological properties. Although few clinical trial studies have been performed on drug delivery and photosensitization with lasers, GNPs have not yet received Food and Drug Administration approval for use in radiotherapy. The sensitization effects of GNPs are dependent on their concentration in cells and x-ray energy deposition during radiotherapy. Notably, some limitations related to the properties of the GNPs, including their size, shape, surface charge, and ligands, and the radiation source energy should be resolved. At the first, this review focuses on some of the challenges of using GNPs as radiosensitizers and some biases among in vitro/in vivo, Monte Carlo, and clinical studies. Then, we discuss the challenges in the clinical translation of GNPs as radiosensitizers for radiotherapy and proposes feasible solutions. And finally, we suggest that certain areas be considered in future research. This article is categorized under: Therapeutic Approaches and Drug Discovery > NA.

放射治疗是与手术、化疗相结合的癌症治疗的必然选择。然而,高剂量的放射治疗同时杀死正常细胞和肿瘤细胞。此外,一些肿瘤细胞对放疗有耐药性。近年来,高z纳米材料作为放射治疗的增敏剂受到了许多研究者的关注。其中,金纳米粒子(GNPs)因其具有良好的物理、化学和生物特性而显示出巨大的潜力。虽然很少有关于激光给药和光敏化的临床试验研究,但GNPs尚未获得食品和药物管理局批准用于放射治疗。GNPs的致敏作用取决于其在细胞中的浓度和放疗期间的x射线能量沉积。值得注意的是,GNPs的一些特性限制,包括它们的大小、形状、表面电荷、配体和辐射源能量,应该得到解决。首先,这篇综述着重于使用GNPs作为放射增敏剂的一些挑战,以及在体外/体内、蒙特卡罗和临床研究中的一些偏差。然后,我们讨论了GNPs作为放射增敏剂在临床转化中的挑战,并提出了可行的解决方案。最后,我们建议在未来的研究中考虑某些领域。本文分类如下:治疗方法和药物发现>na。
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引用次数: 1
Magnetite-based Janus nanoparticles, their synthesis and biomedical applications. 基于磁铁矿的Janus纳米颗粒,它们的合成和生物医学应用。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-11-01 Epub Date: 2023-06-04 DOI: 10.1002/wnan.1908
Mozhdeh Madadi, Sepideh Khoee

The advent of Janus nanoparticles has been a great breakthrough in the emerging field of nanomaterials. Janus nanoparticles refer to a single structure with two distinct chemical functions on either side. Owing to their asymmetric structures, they can be utilized in a variety of applications where monomorphic particles are insufficient. In the last decade, a wide variety of materials have been employed to fabricate Janus nanoparticles, and due to the great advantages of magnetite (Iron-oxide) NPs, they have been considered as one of the best candidates. With the main benefit of magnetic controlling, magnetite Janus nanoparticles fulfill great promises, especially in biomedical areas such as bioimaging, cancer therapies, theranostics, and biosensing. The intrinsic characteristics of magnetite Janus nanoparticles (MJNPs) even hold great potential in magnetite Janus forms of micro-/nanomotors. Despite the great interest and potential in magnetic Janus NPs, the need for a comprehensive review on MJNPs with a concentration on magnetite NPs has been overlooked. Herein, we present recent advancements in the magnetite-based Janus nanoparticles in the flourishing field of biomedicine. First, the synthesis and fabrication methods of Janus nanoparticles are discussed. Then we will delve into their intriguing biomedical applications, with a separate section for magnetite Janus micro-/nanomotors in biomedicine. And finally, the challenges and future outlook are provided. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Diagnostic Nanodevices Diagnostic Tools > In Vitro Nanoparticle-Based Sensing.

Janus纳米粒子的出现是纳米材料新兴领域的一个重大突破。Janus纳米颗粒指的是一种单一结构,其两侧具有两种不同的化学功能。由于它们的不对称结构,它们可以在单态粒子不足的各种应用中使用。在过去的十年里,各种各样的材料被用来制造Janus纳米颗粒,由于磁铁矿(氧化铁)NPs的巨大优势,它们被认为是最好的候选者之一。由于具有磁性控制的主要优点,Janus纳米颗粒在生物医学领域(如生物成像、癌症治疗、治疗学和生物传感)具有很大的前景。磁性Janus纳米颗粒(MJNPs)的固有特性甚至在磁性Janus形式的微/纳米马达中具有很大的潜力。尽管人们对磁性Janus NPs有着极大的兴趣和潜力,但对以磁铁矿NPs为重点的MJNPs进行全面综述的必要性一直被忽视。在此,我们介绍了磁铁矿基Janus纳米颗粒在蓬勃发展的生物医学领域的最新进展。首先,讨论了Janus纳米粒子的合成和制备方法。然后,我们将深入研究其有趣的生物医学应用,与磁铁矿Janus微/纳米马达在生物医学中的单独部分。最后,提出了挑战和未来展望。本文分类如下:治疗方法和药物发现>新兴技术纳米技术生物学方法>生物学诊断工具中的纳米级系统>诊断纳米器件诊断工具>体外纳米颗粒传感。
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引用次数: 1
Conducting polymer-based nanostructured materials for brain-machine interfaces. 用于脑机接口的导电聚合物基纳米结构材料。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-01 Epub Date: 2023-05-04 DOI: 10.1002/wnan.1895
Yasamin Ziai, Seyed Shahrooz Zargarian, Chiara Rinoldi, Paweł Nakielski, Antonella Sola, Massimiliano Lanzi, Yen Bach Truong, Filippo Pierini

As scientists discovered that raw neurological signals could translate into bioelectric information, brain-machine interfaces (BMI) for experimental and clinical studies have experienced massive growth. Developing suitable materials for bioelectronic devices to be used for real-time recording and data digitalizing has three important necessitates which should be covered. Biocompatibility, electrical conductivity, and having mechanical properties similar to soft brain tissue to decrease mechanical mismatch should be adopted for all materials. In this review, inorganic nanoparticles and intrinsically conducting polymers are discussed to impart electrical conductivity to systems, where soft materials such as hydrogels can offer reliable mechanical properties and a biocompatible substrate. Interpenetrating hydrogel networks offer more mechanical stability and provide a path for incorporating polymers with desired properties into one strong network. Promising fabrication methods, like electrospinning and additive manufacturing, allow scientists to customize designs for each application and reach the maximum potential for the system. In the near future, it is desired to fabricate biohybrid conducting polymer-based interfaces loaded with cells, giving the opportunity for simultaneous stimulation and regeneration. Developing multi-modal BMIs, Using artificial intelligence and machine learning to design advanced materials are among the future goals for this field. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.

随着科学家们发现原始神经信号可以转化为生物电信息,用于实验和临床研究的脑机接口(BMI)经历了巨大的增长。为用于实时记录和数据数字化的生物电子设备开发合适的材料有三个重要的必要条件。所有材料都应采用生物相容性、导电性和类似于软脑组织的机械性能,以减少机械失配。在这篇综述中,讨论了无机纳米颗粒和固有导电聚合物,以赋予系统导电性,其中水凝胶等软材料可以提供可靠的机械性能和生物相容性基质。互穿水凝胶网络提供了更多的机械稳定性,并为将具有所需性能的聚合物结合到一个强大的网络中提供了一条途径。有前景的制造方法,如静电纺丝和增材制造,使科学家能够为每种应用定制设计,并达到系统的最大潜力。在不久的将来,人们希望制造负载有细胞的生物杂化导电聚合物基界面,为同时刺激和再生提供机会。开发多模态BMI,利用人工智能和机器学习设计先进材料是该领域未来的目标之一。这篇文章分类在:治疗方法和药物发现>神经疾病的纳米医学。
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引用次数: 2
Nanotechnology enabled radioprotectants to reduce space radiation-induced reactive oxidative species. 纳米技术使放射性保护剂能够减少空间辐射诱导的反应性氧化物种。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-01 Epub Date: 2023-05-16 DOI: 10.1002/wnan.1896
Balaashwin Babu, Shreya Pawar, Agastya Mittal, Elayaraja Kolanthai, Craig J Neal, Melanie Coathup, Sudipta Seal

Interest in space exploration has seen substantial growth following recent launch and operation of modern space technologies. In particular, the possibility of travel beyond low earth orbit is seeing sustained support. However, future deep space travel requires addressing health concerns for crews under continuous, longer-term exposure to adverse environmental conditions. Among these challenges, radiation-induced health issues are a major concern. Their potential to induce chronic illness is further potentiated by the microgravity environment. While investigations into the physiological effects of space radiation are still under investigation, studies on model ionizing radiation conditions, in earth and micro-gravity conditions, can provide needed insight into relevant processes. Substantial formation of high, sustained reactive oxygen species (ROS) evolution during radiation exposure is a clear threat to physiological health of space travelers, producing indirect damage to various cell structures and requiring therapeutic address. Radioprotection toward the skeletal system components is essential to astronaut health, due to the high radio-absorption cross-section of bone mineral and local hematopoiesis. Nanotechnology can potentially function as radioprotectant and radiomitigating agents toward ROS and direct radiation damage. Nanoparticle compositions such as gold, silver, platinum, carbon-based materials, silica, transition metal dichalcogenides, and ceria have all shown potential as viable radioprotectants to mitigate space radiation effects with nanoceria further showing the ability to protect genetic material from oxidative damage in several studies. As research into space radiation-induced health problems develops, this review intends to provide insights into the nanomaterial design to ameliorate pathological effects from ionizing radiation exposure. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

随着现代空间技术最近的发射和运行,人们对太空探索的兴趣大幅增长。特别是,穿越近地轨道的可能性得到了持续的支持。然而,未来的深空旅行需要解决机组人员在持续、长期暴露于不利环境条件下的健康问题。在这些挑战中,辐射引起的健康问题是一个主要关切。微重力环境进一步增强了它们诱发慢性疾病的潜力。虽然对空间辐射的生理影响的调查仍在调查中,但对地球和微重力条件下的电离辐射模型条件的研究可以对相关过程提供必要的见解。辐射暴露期间大量形成高、持续的活性氧(ROS)进化,对太空旅行者的生理健康构成明显威胁,对各种细胞结构产生间接损伤,需要治疗。由于骨矿物质和局部造血的高无线电吸收截面,对骨骼系统组件的辐射防护对宇航员的健康至关重要。纳米技术可能对ROS和直接辐射损伤起到辐射保护剂和辐射减轻剂的作用。纳米颗粒组合物,如金、银、铂、碳基材料、二氧化硅、过渡金属二硫属化物和二氧化铈,都显示出作为可行的放射性保护剂的潜力,以减轻空间辐射效应。在几项研究中,纳米二氧化铈进一步显示出保护遗传物质免受氧化损伤的能力。随着空间辐射引发的健康问题研究的发展,这篇综述旨在为纳米材料的设计提供见解,以改善电离辐射暴露的病理影响。本文分类如下:治疗方法和药物发现>新兴技术生物学的纳米技术方法>生物学中的纳米系统生物学的纳米科技方法>纳米治疗方法和药品发现中的细胞>肿瘤疾病的纳米医学。
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引用次数: 1
Organoids technology for advancing the clinical translation of cancer nanomedicine. 推进癌症纳米医学临床转化的类器官技术。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-01 Epub Date: 2023-04-23 DOI: 10.1002/wnan.1892
Dong-Kun Zhao, Jie Liang, Xiao-Yi Huang, Song Shen, Jun Wang

The past decades have witnessed the rapid development and widespread application of nanomedicines in cancer treatment; however, the clinical translation of experimental findings has been low, as evidenced by the low percentage of commercialized nanomedicines. Incomplete understanding of nanomedicine-tumor interactions and inappropriate evaluation models are two important challenges limiting the clinical translation of cancer nanomedicines. Currently, nanomedicine-tumor interaction and therapeutic effects are mainly investigated using cell lines or mouse models, which do not recapitulate the complex tumor microenvironment in human patients. Thus, information obtained from cell lines and mouse models cannot provide adequate guidance for the rational redesign of nanomedicine. Compared with other preclinical models, tumor organoids constructed from patient-derived tumor tissues are superior in retaining the key histopathological, genetic, and phenotypic features of the parent tumor. We speculate that organoid technology would help elucidate nanomedicine-tumor interaction in the tumor microenvironment and guide the design of nanomedicine, making it a reliable tool to accurately predict drug responses in patients with cancer. This review highlighted the advantages of drug delivery systems in cancer treatment, challenges limiting the clinical translation of antitumor nanomedicines, and potential application of patient-derived organoids (PDO) in nanomedicine. We propose that combining organoids and nanotechnology would facilitate the development of safe and effective cancer nanomedicines and accelerate their clinical application. This review discussed the potential translational value of integrative research using organoids and cancer nanomedicine. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

在过去的几十年里,纳米药物在癌症治疗中得到了快速发展和广泛应用;然而,实验结果的临床转化率一直很低,商业化纳米药物的比例很低就是明证。对纳米药物-肿瘤相互作用的不完全理解和不适当的评估模型是限制癌症纳米药物临床转化的两个重要挑战。目前,纳米药物与肿瘤的相互作用和治疗效果主要使用细胞系或小鼠模型进行研究,这些模型并没有概括人类患者复杂的肿瘤微环境。因此,从细胞系和小鼠模型中获得的信息无法为纳米医学的合理重新设计提供充分的指导。与其他临床前模型相比,由患者来源的肿瘤组织构建的肿瘤类器官在保留母体肿瘤的关键组织病理学、遗传和表型特征方面具有优势。我们推测,类器官技术将有助于阐明纳米药物与肿瘤微环境中的相互作用,并指导纳米药物的设计,使其成为准确预测癌症患者药物反应的可靠工具。这篇综述强调了药物递送系统在癌症治疗中的优势,限制抗肿瘤纳米药物临床转化的挑战,以及患者来源的类器官(PDO)在纳米药物中的潜在应用。我们建议将类器官和纳米技术结合起来,将有助于开发安全有效的癌症纳米药物,并加速其临床应用。这篇综述讨论了利用类器官和癌症纳米医学进行综合研究的潜在转化价值。本文分类为:纳米技术生物学方法>生物学中的纳米系统治疗方法和药物发现>肿瘤疾病的纳米医学。
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引用次数: 1
The clinical progress and challenges of mRNA vaccines. 信使核糖核酸疫苗的临床进展和挑战。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-01 Epub Date: 2023-04-24 DOI: 10.1002/wnan.1894
Meng-Zhen Yu, Nan-Nan Wang, Jia-Qing Zhu, Yao-Xin Lin

Owing to the breakthroughs in the prevention and control of the COVID-19 pandemic, messenger RNA (mRNA)-based vaccines have emerged as promising alternatives to conventional vaccine approaches for infectious disease prevention and anticancer treatments. Advantages of mRNA vaccines include flexibility in designing and manipulating antigens of interest, scalability in rapid response to new variants, ability to induce both humoral and cell-mediated immune responses, and ease of industrialization. This review article presents the latest advances and innovations in mRNA-based vaccines and their clinical translations in the prevention and treatment of infectious diseases or cancers. We also highlight various nanoparticle delivery platforms that contribute to their success in clinical translation. Current challenges related to mRNA immunogenicity, stability, and in vivo delivery and the strategies for addressing them are also discussed. Finally, we provide our perspectives on future considerations and opportunities for applying mRNA vaccines to fight against major infectious diseases and cancers. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.

由于在预防和控制新冠肺炎大流行方面取得了突破,基于信使RNA(mRNA)的疫苗已成为传染病预防和抗癌治疗的传统疫苗方法的有前途的替代品。信使核糖核酸疫苗的优点包括设计和操纵感兴趣抗原的灵活性、对新变种的快速反应的可扩展性、诱导体液和细胞介导的免疫反应的能力以及易于工业化。这篇综述文章介绍了基于信使核糖核酸的疫苗的最新进展和创新,以及它们在传染病或癌症预防和治疗中的临床应用。我们还重点介绍了各种纳米颗粒递送平台,这些平台有助于它们在临床翻译中的成功。还讨论了当前与mRNA免疫原性、稳定性和体内递送相关的挑战以及解决这些挑战的策略。最后,我们提供了我们对应用信使核糖核酸疫苗对抗主要传染病和癌症的未来考虑和机会的看法。本文分类如下:治疗方法和药物发现>新兴技术治疗方法和药品发现>传染病纳米医学生物学启发的纳米材料>脂质基结构。
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引用次数: 2
Multi-ligand functionalized blood-to-tumor sequential targeting strategies in the field of glioblastoma nanomedicine. 胶质母细胞瘤纳米医学领域的多配体功能化血液到肿瘤的顺序靶向策略。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-01 Epub Date: 2023-04-25 DOI: 10.1002/wnan.1893
Cláudia Martins, Bruno Sarmento

Glioblastoma (GBM) is an unmet clinical need characterized by a standard of care (SOC) 5-year survival rate of only 5%, and a treatment mostly palliative. Significant hurdles in GBM therapies include an effective penetration of therapeutics through the brain protective barrier, namely the blood-brain barrier (BBB), and a successful therapeutic delivery to brain-invading tumor cells post-BBB crossing. These hurdles, along with the poor prognosis and critical heterogeneity of the disease, have shifted attention to treatment modalities with capacity to precisely and sequentially target (i) BBB cells, inducing blood-to-brain transport, and (ii) GBM cells, leading to a higher therapeutic accumulation at the tumor site. This sequential targeting allows therapeutic molecules to reach the brain parenchyma and compromise molecular processes that support tumor cell invasion. Besides improving formulation and pharmacokinetics constraints of drugs, nanomedicines offer the possibility of being surface functionalized with multiple possibilities of targeting ligands, while delivering the desired therapeutic cargos to the biological sites of interest. Targeting ligands exploit the site-specific expression or overexpression of specific molecules on BBB and GBM cells, triggering brain plus tumor transport. Since the efficacy of single-ligand functionalized nanomedicines is limited due to the GBM anatomical site (brain) and disease complexity, this review presents an overview of multi-ligand functionalized, BBB and GBM sequentially- and dual-targeted nanomedicines reported in literature over the last 10 years. The role of the BBB in GBM progression, treatment options, and the multiple possibilities of currently available targeting ligands will be summarized. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

胶质母细胞瘤(GBM)是一种未满足的临床需求,其特征是标准护理(SOC)的5年生存率仅为5%,并且治疗主要是姑息性的。GBM治疗中的重大障碍包括治疗剂有效穿透大脑保护屏障,即血脑屏障(BBB),以及在穿过血脑屏障后成功地向侵入大脑的肿瘤细胞提供治疗。这些障碍,加上该疾病的不良预后和严重的异质性,已将注意力转移到能够精确和顺序靶向(i)血脑屏障细胞,诱导血脑转运,和(ii)GBM细胞的治疗模式上,导致在肿瘤部位有更高的治疗积累。这种顺序靶向使治疗分子能够到达脑实质,并破坏支持肿瘤细胞侵袭的分子过程。除了改善药物的配方和药代动力学约束外,纳米药物还提供了用多种靶向配体进行表面功能化的可能性,同时将所需的治疗货物输送到感兴趣的生物位点。靶向配体利用特定分子在血脑屏障和GBM细胞上的位点特异性表达或过表达,触发脑加肿瘤转运。由于GBM的解剖部位(大脑)和疾病复杂性,单配体功能化纳米药物的疗效有限,这篇综述概述了过去10年文献中报道的多配体功能化、BBB和GBM顺序和双靶向纳米药物 年。将总结血脑屏障在GBM进展中的作用、治疗选择以及目前可用的靶向配体的多种可能性。本文分类为:纳米技术生物学方法>生物学中的纳米系统治疗方法和药物发现>肿瘤疾病的纳米医学。
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引用次数: 1
Nanotechnology-empowered therapeutics targeting neurodegenerative diseases. 纳米技术增强了针对神经退行性疾病的治疗。
IF 6.9 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-01 Epub Date: 2023-05-30 DOI: 10.1002/wnan.1907
Zhiren Wang, Karina Marie Gonzalez, Leyla Estrella Cordova, Jianqin Lu

Neurodegenerative diseases are posing pressing health issues due to the high prevalence among aging populations in the 21st century. They are evidenced by the progressive loss of neuronal function, often associated with neuronal necrosis and many related devastating complications. Nevertheless, effective therapeutical strategies to treat neurodegenerative diseases remain a tremendous challenge due to the multisystemic nature and limited drug delivery to the central nervous system. As a result, there is a pressing need to develop effective alternative therapeutics to manage the progression of neurodegenerative diseases. By utilizing the functional reconstructive materials and technologies with specific targeting ability at the nanoscale level, nanotechnology-empowered medicines can transform the therapeutic paradigms of neurodegenerative diseases with minimal systemic side effects. This review outlines the current applications and progresses of the nanotechnology-enabled drug delivery systems to enhance the therapeutic efficacy in treating neurodegenerative diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

由于21世纪老龄化人口中的高发病率,神经退行性疾病正在带来紧迫的健康问题。神经元功能的逐渐丧失证明了这一点,通常与神经元坏死和许多相关的破坏性并发症有关。然而,由于神经退行性疾病的多系统性质和对中枢神经系统的有限药物输送,治疗神经退行性病变的有效治疗策略仍然是一个巨大的挑战。因此,迫切需要开发有效的替代疗法来控制神经退行性疾病的进展。通过利用具有纳米级特定靶向能力的功能重建材料和技术,纳米技术增强的药物可以在系统副作用最小的情况下改变神经退行性疾病的治疗模式。这篇综述概述了纳米技术药物递送系统在提高神经退行性疾病治疗效果方面的最新应用和进展。本文分类为:治疗方法和药物发现>神经疾病纳米医学治疗方法和药品发现>新兴技术。
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引用次数: 0
Pumped and pumpless microphysiological systems to study (nano)therapeutics. 用于研究(纳米)疗法的泵送和无泵微物理系统。
IF 6.9 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-01 Epub Date: 2023-07-18 DOI: 10.1002/wnan.1911
Eun-Jin Lee, Zachary L Krassin, Hasan Erbil Abaci, Gretchen J Mahler, Mandy B Esch

Fluidic microphysiological systems (MPS) are microfluidic cell culture devices that are designed to mimic the biochemical and biophysical in vivo microenvironments of human tissues better than conventional petri dishes or well-plates. MPS-grown tissue cultures can be used for probing new drugs for their potential primary and secondary toxicities as well as their efficacy. The systems can also be used for assessing the effects of environmental nanoparticles and nanotheranostics, including their rate of uptake, biodistribution, elimination, and toxicity. Pumpless MPS are a group of MPS that often utilize gravity to recirculate cell culture medium through their microfluidic networks, providing some advantages, but also presenting some challenges. They can be operated with near-physiological amounts of blood surrogate (i.e., cell culture medium) that can recirculate in bidirectional or unidirectional flow patterns depending on the device configuration. Here we discuss recent advances in the design and use of both pumped and pumpless MPS with a focus on where pumpless devices can contribute to realizing the potential future role of MPS in evaluating nanomaterials. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

流体微物理系统(MPS)是一种微流体细胞培养装置,设计用于比传统的培养皿或孔板更好地模拟人体组织的生物化学和生物物理体内微环境。MPS生长的组织培养物可用于探索新药潜在的主要和次要毒性及其疗效。该系统还可用于评估环境纳米颗粒和纳米治疗药物的影响,包括它们的吸收率、生物分布、消除和毒性。无泵MPS是一组经常利用重力使细胞培养基通过其微流体网络再循环的MPS,提供了一些优势,但也带来了一些挑战。它们可以用接近生理量的血液替代物(即细胞培养基)进行操作,这些血液替代物可以根据设备配置以双向或单向流动模式再循环。在这里,我们讨论了泵送和无泵MPS的设计和使用方面的最新进展,重点是无泵装置在哪些方面可以有助于实现MPS在评估纳米材料方面的潜在未来作用。本文分类在:治疗方法和药物发现>纳米医学新兴技术毒理学和监管问题>纳米材料毒理学。
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引用次数: 0
Noncovalent PEGylation of protein and peptide therapeutics. 蛋白质和肽疗法的非共价PEG化。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-01 Epub Date: 2023-05-03 DOI: 10.1002/wnan.1897
Alexander K Andrianov

Clinical applications of protein therapeutics-an advanced generation of drugs characterized by high biological specificity-are rapidly expanding. However, their development is often impeded by unfavorable pharmacokinetic profiles and largely relies on the use of drug delivery systems to prolong their in vivo half-life and suppress undesirable immunogenicity. Although a commercially established PEGylation technology based on protein conjugation with poly(ethylene glycol) (PEG)-protective steric shield resolves some of the challenges, the search for alternatives continues. Noncovalent PEGylation, which mainly relies on multivalent (cooperative) interactions and high affinity (host-guest) complexes formed between protein and PEG offers a number of potential advantages. Among them are dynamic or reversible protection of the protein with minimal loss of biological activity, drastically lower manufacturing costs, "mix-and-match" formulations approaches, and expanded scope of PEGylation targets. While a great number of innovative chemical approaches have been proposed in recent years, the ability to effectively control the stability of noncovalently assembled protein-PEG complexes under physiological conditions presents a serious challenge for the commercial development of the technology. In an attempt to identify critical factors affecting pharmacological behavior of noncovalently linked complexes, this Review follows a hierarchical analysis of various experimental techniques and resulting supramolecular architectures. The importance of in vivo administration routes, degradation patterns of PEGylating agents, and a multitude of potential exchange reactions with constituents of physiological compartments are highlighted. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

蛋白质治疗的临床应用——以高生物学特异性为特征的新一代药物——正在迅速扩大。然而,它们的发展往往受到不利的药代动力学特征的阻碍,并且在很大程度上依赖于药物递送系统的使用来延长其体内半衰期并抑制不良的免疫原性。尽管商业上建立的基于蛋白质与聚乙二醇(PEG)保护性立体屏蔽偶联的PEG化技术解决了一些挑战,但替代品的搜索仍在继续。非共价PEG化主要依赖于蛋白质和PEG之间形成的多价(协同)相互作用和高亲和力(宿主-客体)复合物,它提供了许多潜在的优势。其中包括在生物活性损失最小的情况下对蛋白质进行动态或可逆保护、大幅降低制造成本、“混合搭配”配方方法以及扩大聚乙二醇化靶点的范围。尽管近年来提出了大量创新的化学方法,但在生理条件下有效控制非共价组装的蛋白质-PEG复合物的稳定性的能力对该技术的商业开发提出了严峻的挑战。为了确定影响非共价连接复合物药理行为的关键因素,本综述对各种实验技术和由此产生的超分子结构进行了分级分析。强调了体内给药途径、聚乙二醇化剂的降解模式以及与生理区组分的多种潜在交换反应的重要性。本文分类如下:治疗方法和药物发现>新兴技术生物学的纳米技术方法>生物学中的纳米系统治疗方法和药品发现>肿瘤疾病的纳米医学。
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Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
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