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Tumor microenvironment-regulating nanomedicine design to fight multi-drug resistant tumors. 肿瘤微环境调节纳米药物设计对抗多重耐药肿瘤。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1002/wnan.1842
Qinqin Xu, Xinyue Lan, Huimin Lin, Qiye Xi, Manchun Wang, Xiaolong Quan, Guangyu Yao, Zhiqiang Yu, Yongxia Wang, Meng Yu

The tumor microenvironment (TME) is a very cunning system that enables tumor cells to escape death post-traditional antitumor treatments through the comprehensive effect of different factors, thereby leading to drug resistance. Deep insights into TME characteristics and tumor resistance encourage the construction of nanomedicines that can remodel the TME against drug resistance. Tremendous interest in combining TME-regulation measurement with traditional tumor treatment to fight multidrug-resistant tumors has been inspired by the increasing understanding of the role of TME reconstruction in improving the antitumor efficiency of drug-resistant tumor therapy. This review focuses on the underlying relationships between specific TME characteristics (such as hypoxia, acidity, immunity, microorganisms, and metabolism) and drug resistance in tumor treatments. The exciting antitumor activities strengthened by TME regulation are also discussed in-depth, providing solutions from the perspective of nanomedicine design. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

肿瘤微环境(tumor microenvironment, TME)是一个非常狡猾的系统,它通过不同因素的综合作用,使肿瘤细胞在传统抗肿瘤治疗后逃脱死亡,从而导致耐药。对TME特征和肿瘤耐药性的深入了解鼓励了纳米药物的构建,这些纳米药物可以重塑TME以对抗耐药性。随着对TME重建在提高耐药肿瘤治疗抗肿瘤效率中的作用的认识不断加深,人们对将TME调节测量与传统肿瘤治疗结合起来对抗多药耐药肿瘤产生了极大的兴趣。本文综述了肿瘤治疗中TME特异性特征(如缺氧、酸度、免疫、微生物和代谢)与耐药之间的潜在关系。深入探讨了TME调控增强的令人兴奋的抗肿瘤活性,并从纳米药物设计的角度提出了解决方案。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物发现>肿瘤疾病的纳米医学纳米技术生物学方法>生物学中的纳米级系统。
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引用次数: 6
Nano-diagnostics as an emerging platform for oral cancer detection: Current and emerging trends. 纳米诊断作为口腔癌检测的新兴平台:当前和新兴趋势。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1002/wnan.1830
Debolina Chakraborty, Debayan Ghosh, Sanjit Kumar, David Jenkins, Natarajan Chandrasekaran, Amitava Mukherjee

Globally, oral cancer kills an estimated 150,000 individuals per year, with 300,000 new cases being diagnosed annually. The high incidence rate of oral cancer among the South-Asian and American populations is majorly due to overuse of tobacco, alcohol, and poor dental hygiene. Additionally, socio-economic issues and lack of general awareness delay the primary screening of the disease. The availability of early screening techniques for oral cancer can help in carving out a niche for accurate disease prognosis and also its prevention. However, conventional diagnostic approaches and therapeutics are still far from optimal. Thus, enhancing the analytical performance of diagnostic platforms in terms of specificity and precision can help in understanding the disease progression paradigm. Fabrication of efficient nanoprobes that are sensitive, noninvasive, cost-effective, and less labor-intensive can reduce the global cancer burden. Recent advances in optical, electrochemical, and spectroscopy-based nano biosensors that employ noble and superparamagnetic nanoparticles, have been proven to be extremely efficient. Further, these sensitive nanoprobes can also be employed for predicting disease relapse after chemotherapy, when the majority of the biomarker load is eliminated. Herein, we provide the readers with a brief summary of conventional and new-age oral cancer detection techniques. A comprehensive understanding of the inherent challenges associated with conventional oral cancer detection techniques is discussed. We also elaborate on how nanoparticles have shown tremendous promise and effectiveness in radically transforming the approach toward oral cancer detection. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices Diagnostic Tools > In Vitro Nanoparticle-Based Sensing.

在全球范围内,口腔癌每年导致约15万人死亡,每年有30万新病例被诊断出来。口腔癌在南亚和美洲人群中的高发病率主要是由于过度使用烟草、酒精和不良的口腔卫生。此外,社会经济问题和缺乏普遍认识推迟了该病的初步筛查。口腔癌早期筛查技术的可用性有助于为准确的疾病预后和预防开辟一个利基。然而,传统的诊断方法和治疗方法仍远未达到最佳效果。因此,在特异性和精确性方面提高诊断平台的分析性能有助于理解疾病进展范式。制造高效、灵敏、无创、低成本、低劳动密集型的纳米探针可以减轻全球癌症负担。基于光学、电化学和光谱的纳米生物传感器的最新进展已被证明是非常有效的,这些传感器采用了贵金属和超顺磁性纳米颗粒。此外,这些敏感的纳米探针还可以用于预测化疗后的疾病复发,当大多数生物标志物负荷被消除时。在此,我们为读者提供传统和新时代口腔癌检测技术的简要总结。全面了解与传统口腔癌检测技术相关的固有挑战。我们还详细阐述了纳米颗粒如何在彻底改变口腔癌检测方法方面显示出巨大的希望和有效性。本文分类如下:诊断工具>生物传感诊断工具>诊断纳米设备诊断工具>体外纳米颗粒传感。
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引用次数: 8
Electrospun fibers as carriers for topical drug delivery and release in skin bandages and patches for atopic dermatitis treatment. 电纺丝纤维作为治疗特应性皮炎的皮肤绷带和贴剂中局部药物递送和释放的载体。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1002/wnan.1829
Zuzanna J Krysiak, Urszula Stachewicz

The skin is a complex layer system and the most important barrier between the environment and the organism. In this review, we describe some widespread skin problems, with a focus on eczema, which are affecting more and more people all over the world. Most of treatment methods for atopic dermatitis (AD) are focused on increasing skin moisture and protecting from bacterial infection and external irritation. Topical and transdermal treatments have specific requirements for drug delivery. Breathability, flexibility, good mechanical properties, biocompatibility, and efficacy are important for the patches used for skin. Up to today, electrospun fibers are mostly used for wound dressing. Their properties, however, meet the requirements for skin patches for the treatment of AD. Active agents can be incorporated into fibers by blending, coaxial or side-by-side electrospinning, and also by physical absorption post-processing. Drug release from the electrospun membranes is affected by drug and polymer properties and the technique used to combine them into the patch. We describe in detail the in vitro release mechanisms, parameters affecting the drug transport, and their kinetics, including theoretical approaches. In addition, we present the current research on skin patch design. This review summarizes the current extensive know-how on electrospun fibers as skin drug delivery systems, while underlining the advantages in their prospective use as patches for atopic dermatitis. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Emerging Technologies.

皮肤是一个复杂的层状系统,是环境和生物体之间最重要的屏障。在这篇综述中,我们描述了一些普遍存在的皮肤问题,重点是湿疹,这是影响越来越多的人在世界各地。大多数特应性皮炎(AD)的治疗方法集中在增加皮肤水分和防止细菌感染和外部刺激。局部和透皮治疗对药物输送有特殊要求。透气性、柔韧性、良好的机械性能、生物相容性和功效对用于皮肤的贴片很重要。到目前为止,电纺纤维主要用于伤口敷料。然而,它们的性能满足治疗AD的皮肤贴片的要求。活性剂可以通过共混、同轴或并排静电纺丝,也可以通过物理吸收后处理掺入纤维中。药物从电纺丝膜释放受药物和聚合物性质以及将它们结合到贴片中的技术的影响。我们详细描述了体外释放机制,影响药物转运的参数,以及它们的动力学,包括理论方法。此外,我们还介绍了皮肤贴片设计的研究现状。这篇综述总结了目前关于电纺丝纤维作为皮肤药物输送系统的广泛技术,同时强调了其作为特应性皮炎贴剂的潜在优势。本文分类如下:植入材料与外科技术>纳米材料与植入物植入材料与外科技术>纳米技术在组织修复和替代治疗方法和药物发现>新兴技术。
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引用次数: 28
Nano-embedded medical devices and delivery systems in interventional radiology. 介入放射学中的纳米嵌入式医疗设备和传输系统。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 Epub Date: 2022-08-10 DOI: 10.1002/wnan.1841
Erin Marie D San Valentin, Allan John R Barcena, Carleigh Klusman, Benjamin Martin, Marites P Melancon

Nanomaterials research has significantly accelerated the development of the field of vascular and interventional radiology. The incorporation of nanoparticles with unique and functional properties into medical devices and delivery systems has paved the way for the creation of novel diagnostic and therapeutic procedures for various clinical disorders. In this review, we discuss the advancements in the field of interventional radiology and the role of nanotechnology in maximizing the benefits and mitigating the disadvantages of interventional radiology theranostic procedures. Several nanomaterials have been studied to improve the efficacy of interventional radiology interventions, reduce the complications associated with medical devices, improve the accuracy and efficiency of drug delivery systems, and develop innovative imaging modalities. Here, we summarize the recent progress in the development of medical devices and delivery systems that link nanotechnology in vascular and interventional radiology. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease.

纳米材料研究大大加快了血管和介入放射学领域的发展。将具有独特功能特性的纳米颗粒融入医疗设备和传输系统,为各种临床疾病的新型诊断和治疗程序的开发铺平了道路。在这篇综述中,我们将讨论介入放射学领域的进展以及纳米技术在最大限度地发挥介入放射学治疗程序的优势和减少其劣势方面所起的作用。为了提高介入放射学干预的效果、减少与医疗设备相关的并发症、提高给药系统的准确性和效率以及开发创新的成像模式,已经对多种纳米材料进行了研究。在此,我们总结了将纳米技术应用于血管和介入放射学的医疗设备和给药系统开发的最新进展。本文归类于诊断工具 > 纳米诊断设备 诊断工具 > 体内纳米诊断和成像 治疗方法和药物发现 > 用于心血管疾病的纳米医学。
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引用次数: 9
Immunomodulation in age-related disorders and nanotechnology interventions. 年龄相关疾病的免疫调节和纳米技术干预。
IF 6.9 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 Epub Date: 2022-08-10 DOI: 10.1002/wnan.1840
Uday Chintapula, Tanmayee Chikate, Deepsundar Sahoo, Amie Kieu, Ingrid D Guerrero Rodriguez, Kytai T Nguyen, Daniel Trott

Recently, the aging population has increased exponentially around the globe bringing more challenges to improve quality of life in those populations while reducing the economic burden on healthcare systems. Aging is associated with changes in the immune system culminating in detrimental effects such as immune dysfunction, immunosenescence, and chronic inflammation. Age-related decline of immune functions is associated with various pathologies including cardiovascular, autoimmune, neurodegenerative, and infectious diseases to name a few. Conventional treatment addresses the onset of age-related diseases by early detection of risk factors, administration of vaccines as preventive care, immunomodulatory treatment, and other dietary supplements. However, these approaches often come with systemic side-effects, low bioavailability of therapeutic agents, and poor outcomes seen in the elderly. Recent innovations in nanotechnology have led to the development of novel biomaterials/nanomaterials, which explore targeted drug delivery and immunomodulatory interactions in vivo. Current nanotechnology-based immunomodulatory approaches that have the potential to be used as therapeutic interventions for some prominent age-related diseases are discussed here. Finally, we explore challenges and future aspects of nanotechnology in the treatments of age-related disorders to improve quality of life in the elderly. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

最近,全球老龄化人口呈指数级增长,在降低医疗系统经济负担的同时,为提高这些人口的生活质量带来了更多挑战。衰老与免疫系统的变化有关,最终导致免疫功能障碍、免疫衰老和慢性炎症等有害影响。与年龄相关的免疫功能下降与各种疾病有关,包括心血管疾病、自身免疫性疾病、神经退行性疾病和传染病等。常规治疗通过早期发现风险因素、接种疫苗作为预防性护理、免疫调节治疗和其他膳食补充剂来解决与年龄相关的疾病的发病问题。然而,这些方法往往会带来全身副作用、治疗剂的生物利用度低以及老年人的不良结果。纳米技术的最新创新导致了新型生物材料/纳米材料的开发,这些材料探索了体内靶向药物递送和免疫调节相互作用。本文讨论了目前基于纳米技术的免疫调节方法,这些方法有可能被用作一些与年龄相关的突出疾病的治疗干预措施。最后,我们探讨了纳米技术在治疗年龄相关疾病方面的挑战和未来方面,以提高老年人的生活质量。本文分类为:治疗方法和药物发现>心血管疾病的纳米医学治疗方法和药品发现>神经疾病的纳米药物治疗方法和新药发现>新兴技术。
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引用次数: 0
Engineering gold nanoparticles for molecular diagnostics and biosensing. 用于分子诊断和生物传感的工程金纳米颗粒。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1002/wnan.1836
Beatriz B Oliveira, Daniela Ferreira, Alexandra R Fernandes, Pedro Viana Baptista

Advances in nanotechnology and medical science have spurred the development of engineered nanomaterials and nanoparticles with particular focus on their applications in biomedicine. In particular, gold nanoparticles (AuNPs) have been the focus of great interest, due to their exquisite intrinsic properties, such as ease of synthesis and surface functionalization, tunable size and shape, lack of acute toxicity and favorable optical, electronic, and physicochemical features, which possess great value for application in biodetection and diagnostics purposes, including molecular sensing, photoimaging, and application under the form of portable and simple biosensors (e.g., lateral flow immunoassays that have been extensively exploited during the current COVID-19 pandemic). We shall discuss the main properties of AuNPs, their synthesis and conjugation to biorecognition moieties, and the current trends in sensing and detection in biomedicine and diagnostics. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

纳米技术和医学科学的进步促进了工程纳米材料和纳米粒子的发展,尤其侧重于它们在生物医学中的应用。特别是,金纳米颗粒(AuNPs)由于其精致的内在特性,如易于合成和表面功能化,可调节的大小和形状,缺乏急性毒性和良好的光学,电子和物理化学特性,在生物检测和诊断目的中具有很大的应用价值,包括分子传感,光电成像,以及在便携式和简单的生物传感器(例如,在当前COVID-19大流行期间已被广泛利用的侧流免疫测定法)。我们将讨论AuNPs的主要性质,它们的合成和缀合到生物识别部分,以及目前在生物医学和诊断传感和检测方面的发展趋势。本文分类如下:诊断工具>生物传感诊断工具>基于体外纳米颗粒的传感诊断工具>体内纳米诊断和成像。
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引用次数: 8
Recent developments in biosensing methods for extracellular vesicle protein characterization. 细胞外囊泡蛋白表征生物传感方法的最新进展。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1002/wnan.1839
Jugal Suthar, Marissa Taub, Randy P Carney, Gareth R Williams, Stefan Guldin

Research into extracellular vesicles (EVs) has grown significantly over the last few decades with EVs being widely regarded as a source of biomarkers for human health and disease with massive clinical potential. Secreted by every cell type in the body, EVs report on the internal cellular conditions across all tissue types. Their presence in readily accessible biofluids makes the potential of EV biosensing highly attractive as a noninvasive diagnostic platform via liquid biopsies. However, their small size (50-250 nm), inherent heterogeneity, and the complexity of the native biofluids introduce challenges for effective characterization, thus, limiting their clinical utility. This has led to a surge in the development of various novel EV biosensing techniques, with capabilities beyond those of conventional methods that have been directly transferred from cell biology. In this review, key detection principles used for EV biosensing are summarized, with a focus on some of the most recent and fundamental developments in the field over the last 5 years. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing.

在过去的几十年里,对细胞外囊泡(EVs)的研究得到了显著的发展,EVs被广泛认为是人类健康和疾病的生物标志物来源,具有巨大的临床潜力。EVs由体内每种细胞类型分泌,报告所有组织类型的内部细胞状况。它们存在于易于获取的生物体液中,这使得EV生物传感作为一种通过液体活检的无创诊断平台具有很高的吸引力。然而,它们的小尺寸(50-250纳米)、固有的异质性和天然生物流体的复杂性为有效表征带来了挑战,从而限制了它们的临床应用。这导致了各种新型EV生物传感技术的发展激增,其能力超出了直接从细胞生物学转移过来的传统方法。本文综述了电动汽车生物传感的关键检测原理,重点介绍了近5年来该领域的一些最新和基本进展。本文分类如下:诊断工具>生物传感诊断工具>体外纳米颗粒传感。
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引用次数: 5
Isolation and characterization of extracellular vesicles and future directions in diagnosis and therapy. 细胞外囊泡的分离和表征以及诊断和治疗的未来方向。
IF 6.9 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 Epub Date: 2022-07-27 DOI: 10.1002/wnan.1835
Karina P De Sousa, Izadora Rossi, Mahamed Abdullahi, Marcel Ivan Ramirez, Dan Stratton, Jameel Malhador Inal

Extracellular vesicles (EVs) are a unique and heterogeneous class of lipid bilayer nanoparticles secreted by most cells. EVs are regarded as important mediators of intercellular communication in both prokaryotic and eukaryotic cells due to their ability to transfer proteins, lipids and nucleic acids to recipient cells. In addition to their physiological role, EVs are recognized as modulators in pathological processes such as cancer, infectious diseases, and neurodegenerative disorders, providing new potential targets for diagnosis and therapeutic intervention. For a complete understanding of EVs as a universal cellular biological system and its translational applications, optimal techniques for their isolation and characterization are required. Here, we review recent progress in those techniques, from isolation methods to characterization techniques. With interest in therapeutic applications of EVs growing, we address fundamental points of EV-related cell biology, such as cellular uptake mechanisms and their biodistribution in tissues as well as challenges to their application as drug carriers or biomarkers for less invasive diagnosis or as immunogens. This article is categorized under: Diagnostic Tools > Biosensing Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

细胞外囊泡(EVs)是大多数细胞分泌的一类独特的异构脂质双层纳米颗粒。由于具有将蛋白质、脂质和核酸转移到受体细胞的能力,EVs 被认为是原核细胞和真核细胞中细胞间通信的重要媒介。除了生理作用外,EVs 还被认为是癌症、传染病和神经退行性疾病等病理过程的调节剂,为诊断和治疗干预提供了新的潜在靶点。为了全面了解作为一种通用细胞生物系统的 EVs 及其转化应用,需要有最佳的 EVs 分离和表征技术。在此,我们回顾了这些技术从分离方法到表征技术的最新进展。随着人们对 EVs 治疗应用的兴趣与日俱增,我们探讨了 EV 相关细胞生物学的基本要点,如细胞摄取机制和它们在组织中的生物分布,以及它们作为药物载体或生物标记物用于微创诊断或作为免疫原所面临的挑战。本文归类于诊断工具 > 生物传感 治疗方法与新药开发 > 用于肿瘤疾病的纳米医学 治疗方法与新药开发 > 用于传染病的纳米医学。
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引用次数: 0
Rethinking nanoparticulate polymer-drug conjugates for cancer theranostics. 重新思考纳米聚合物-药物偶联物在癌症治疗中的应用。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1002/wnan.1828
Yaoqi Wang, Heming Xia, Binlong Chen, Yiguang Wang

Polymer-drug conjugates (PDCs) fabricated as nanoparticles have hogged the limelight in cancer theranostics in the past decade. Many researchers have devoted to developing novel and efficient polymeric drug delivery system since the first generation of poly(N-[2-hydroxypropyl]methacrylamide) copolymer-drug conjugates. However, none of them has been approved for chemotherapy in clinic. An ideal PDC nanoparticle for cancer theranostics should possess several properties, including prolonged circulation in blood, sufficient accumulation and internalization in tumors, and efficient drug release in target sites. To achieve these goals, it is important to rationally design the nanoparticulate PDCs based on circulation, accumulation, penetration, internalization, and drug release (CAPIR) cascade. Specifically, CAPIR cascades are divided into five steps: (1) circulation in the vascular compartment without burst release, (2) accumulation in tumors via enhanced permeability and retention effect, (3) subsequent penetration into the deep regions of tumors, (4) internalization into tumor cells, and (5) release of drugs as free molecules to exert their pharmacological effects. In this review, we focus on the development and novel approaches of nanoparticulate PDCs based on CAPIR cascade, and provide an outlook on future clinical application. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

在过去的十年中,聚合物-药物偶联物(PDCs)以纳米粒子的形式制造成为癌症治疗领域的焦点。自第一代聚(N-[2-羟丙基]甲基丙烯酰胺)共聚物-药物偶联物问世以来,许多研究人员致力于开发新型高效的聚合物给药系统。然而,它们都没有被批准用于临床化疗。用于癌症治疗的理想PDC纳米颗粒应具有以下几个特性:在血液中循环时间长,在肿瘤中有充分的蓄积和内化,以及在靶点有效的药物释放。为了实现这些目标,合理设计基于循环、积累、渗透、内化和药物释放(CAPIR)级联的纳米粒PDCs至关重要。具体来说,CAPIR级联可分为五个步骤:(1)在血管间室中循环而不释放;(2)通过增强渗透性和滞留作用在肿瘤中积累;(3)随后渗透到肿瘤深部;(4)内化到肿瘤细胞中;(5)以自由分子形式释放药物以发挥其药理作用。本文综述了基于CAPIR级联的纳米粒PDCs的研究进展和新方法,并对其临床应用前景进行了展望。本文分类如下: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: 5
Nanoparticles for vaccine and gene therapy: Overcoming the barriers to nucleic acid delivery. 用于疫苗和基因治疗的纳米颗粒:克服核酸传递的障碍。
IF 8.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-11-01 DOI: 10.1002/wnan.1809
Lara M Mollé, Cameron H Smyth, Daniel Yuen, Angus P R Johnston

Nucleic acid therapeutics can be used to control virtually every aspect of cell behavior and therefore have significant potential to treat genetic disorders, infectious diseases, and cancer. However, while clinically approved to treat a small number of diseases, the full potential of nucleic acid therapeutics is hampered by inefficient delivery. Nucleic acids are large, highly charged biomolecules that are sensitive to degradation and so the approaches to deliver these molecules differ significantly from traditional small molecule drugs. Current studies suggest less than 1% of the injected nucleic acid dose is delivered to the target cell in an active form. This inefficient delivery increases costs and limits their use to applications where a small amount of nucleic acid is sufficient. In this review, we focus on two of the major barriers to efficient nucleic acid delivery: (1) delivery to the target cell and (2) transport to the subcellular compartment where the nucleic acids are therapeutically active. We explore how nanoparticles can be modified with targeting ligands to increase accumulation in specific cells, and how the composition of the nanoparticle can be engineered to manipulate or disrupt cellular membranes and facilitate delivery to the optimal subcellular compartments. Finally, we highlight how with intelligent material design, nanoparticle delivery systems have been developed to deliver nucleic acids that silence aberrant genes, correct genetic mutations, and act as both therapeutic and prophylactic vaccines. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.

核酸疗法可以用来控制细胞行为的几乎每一个方面,因此在治疗遗传疾病、传染病和癌症方面具有巨大的潜力。然而,尽管临床批准用于治疗少数疾病,但核酸疗法的全部潜力受到低效递送的阻碍。核酸是大的、高电荷的生物分子,对降解很敏感,因此传递这些分子的方法与传统的小分子药物有很大不同。目前的研究表明,注射的核酸剂量中只有不到1%以活性形式递送到靶细胞。这种低效率的递送增加了成本,并限制了它们在少量核酸就足够的应用中的使用。在这篇综述中,我们将重点关注有效核酸递送的两个主要障碍:(1)递送到靶细胞;(2)转运到核酸具有治疗活性的亚细胞区室。我们探讨了如何用靶向配体修饰纳米颗粒以增加在特定细胞中的积累,以及如何设计纳米颗粒的组成来操纵或破坏细胞膜,并促进递送到最佳的亚细胞区室。最后,我们强调了如何利用智能材料设计,开发纳米颗粒递送系统来递送核酸,使异常基因沉默,纠正基因突变,并作为治疗和预防疫苗。本文分类如下:纳米技术生物学方法>纳米级细胞治疗方法和药物发现>感染性疾病的纳米医学-受生物学启发的纳米材料>基于脂质的结构。
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引用次数: 6
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