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Responsive Nanostructure for Targeted Drug Delivery 靶向药物递送的响应性纳米结构
Pub Date : 2023-02-08 DOI: 10.3390/jnt4010004
Vaishali S. Pawar, P. Maske, Amreen Khan, Arnab Ghosh, Roshan Keshari, Mahek Bhatt, R. Srivastava
Currently, intelligent, responsive biomaterials have been widely explored, considering the fact that responsive biomaterials provide controlled and predictable results in various biomedical systems. Responsive nanostructures undergo reversible or irreversible changes in the presence of a stimulus, and that stimuli can be temperature, a magnetic field, ultrasound, pH, humidity, pressure, light, electric field, etc. Different types of stimuli being used in drug delivery shall be explained here. Recent research progress in the design, development and applications of biomaterials comprising responsive nanostructures is also described here. More emphasis will be given on the various nanostructures explored for the smart stimuli responsive drug delivery at the target site such as wound healing, cancer therapy, inflammation, and pain management in order to achieve the improved efficacy and sustainability with the lowest side effects. However, it is still a big challenge to develop well-defined responsive nanostructures with ordered output; thus, challenges faced during the design and development of these nanostructures shall also be included in this article. Clinical perspectives and applicability of the responsive nanostructures in the targeted drug delivery shall be discussed here.
目前,考虑到反应性生物材料在各种生物医学系统中提供可控和可预测的结果,智能、反应性生物材料已被广泛探索。响应性纳米结构在刺激的存在下经历可逆或不可逆的变化,刺激可以是温度、磁场、超声波、pH值、湿度、压力、光、电场等。在药物传递中使用的不同类型的刺激应在这里解释。本文还介绍了反应性纳米结构生物材料的设计、开发和应用方面的最新研究进展。更多的重点将放在探索各种纳米结构的智能刺激反应药物递送的目标部位,如伤口愈合,癌症治疗,炎症和疼痛管理,以达到提高疗效和可持续性与最低的副作用。然而,开发具有有序输出的、定义良好的响应性纳米结构仍然是一个很大的挑战;因此,在这些纳米结构的设计和开发过程中所面临的挑战也将包括在本文中。本文将讨论反应性纳米结构在靶向药物递送中的临床前景和适用性。
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引用次数: 2
Fluorescent Gold Nanoparticles in Suspension as an Efficient Theranostic Agent for Highly Radio-Resistant Cancer Cells 悬浮的荧光金纳米粒子作为高效治疗癌症细胞的药物
Pub Date : 2023-01-30 DOI: 10.3390/jnt4010003
Sarah Vogel, Alice O’Keefe, Léa Seban, Michael Valceski, E. Engels, Abass Khochaiche, Carolyn Hollis, Michael Lerch, S. Corde, C. Massard, K. Awitor, M. Tehei
Gold nanoparticles are a promising candidate for developing new strategies of therapy against cancer. Due to their high atomic number and relative biocompatibility, they are commonly investigated as radiosensitizers to locally increase the dose of radiotherapy. In order to optimize this radiosensitizing effect, it is necessary to control the positioning of the nanoparticles in the cells. The purpose of this study is to investigate, by means of fluorescent gold nanoparticles in suspension, the dose enhancement on highly radio-resistant cancer cells. These nanoparticles were successfully produced using modern click-chemistry methods, first by attaching a chelating agent Diethylenetriamine pentaacetate benzylamine to L-cysteine, bonding the resulting ligand to a gold core, grafting propargylamine and then utilizing copper-catalyzed azide-alkyne cycloaddition (CuAAC) to fuse AlexaFluor 647 to the ligands. The results of this study prove the success of the reactions to produce a minimally cytotoxic and highly stable nanoparticle suspension that increases the radiosensitivity of gliosarcoma 9L tumor cells, with a 35% increase in cell death using 5 Gy kilovoltage radiation. Their fluorescent functionalization allowed for their simple localization within living cells and detection in vivo post-mortem.
金纳米粒子是开发新的癌症治疗策略的一个很有前途的候选者。由于它们的高原子序数和相对生物相容性,它们通常被研究为局部增加放射治疗剂量的放射增敏剂。为了优化这种放射增敏效果,有必要控制纳米颗粒在细胞中的定位。本研究的目的是通过悬浮液中的荧光金纳米粒子来研究对高度耐辐射的癌症细胞的剂量增强。这些纳米颗粒是使用现代点击化学方法成功生产的,首先是将螯合剂五乙酸二亚乙基三胺苄胺连接到L-半胱氨酸上,将所得配体连接到金芯上,接枝丙炔胺,然后利用铜催化的叠氮化物-炔烃环加成(CuAAC)将AlexaFluor 647融合到配体上。这项研究的结果证明了反应的成功,产生了细胞毒性最小、高度稳定的纳米颗粒悬浮液,该悬浮液提高了胶质肉瘤9L肿瘤细胞的放射敏感性,使用5Gy千伏辐射可使细胞死亡增加35%。它们的荧光功能化使它们能够在活细胞内简单定位并在死后进行体内检测。
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引用次数: 1
Development of Advanced Nanomaterials for Multifunctional Devices: Insights into a Novel Concept of Personalized Medicine 多功能设备先进纳米材料的发展:洞察个性化医疗的新概念
Pub Date : 2023-01-18 DOI: 10.3390/jnt4010002
C. Martinelli, E. Jacchetti
The application of biocompatible nanomaterials to simultaneously detect and provide treatment of a disease is referred to as nanotheranostics [...]
生物相容性纳米材料在同时检测和提供疾病治疗方面的应用被称为纳米治疗学〔…〕
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引用次数: 0
Role of Tunable Gold Nanostructures in Cancer Nanotheranostics: Implications on Synthesis, Toxicity, Clinical Applications and Their Associated Opportunities and Challenges 可调金纳米结构在癌症纳米治疗中的作用:合成、毒性、临床应用及其相关的机遇和挑战
Pub Date : 2023-01-06 DOI: 10.3390/jnt4010001
Akash Kumar, Nabojit Das, R. Rayavarapu
The existing diagnosis and treatment modalities have major limitations related to their precision and capability to understand several stages of disease development. A superior therapeutic system consists of a multifunctional approach in early diagnosis of the disease with a simultaneous progressive cure, using a precise medical approach towards complex treatment. These challenges can be addressed via nanotheranostics and explore suitable approaches to improve health care. Nanotechnology in combination with theranostics as an unconventional platform paved the way for developing novel strategies and modalities leading to diagnosis and therapy for complex disease conditions, ranging from acute to chronic levels. Among the metal nanoparticles, gold nanoparticles are being widely used for theranostics due to their inherent non-toxic nature and plasmonic properties. The unique optical and chemical properties of plasmonic metal nanoparticles along with theranostics have led to a promising era of plausible early detection of disease conditions, and they enable real-time monitoring with enhanced non-invasive or minimally invasive imaging of several ailments. This review aims to highlight the improvement and advancement brought to nanotheranostics by gold nanoparticles in the past decade. The clinical use of the metal nanoparticles in nanotheranostics is explained, along with the future perspectives on addressing the key applications related to diagnostics and therapeutics, respectively. The scope of gold nanoparticles and their realistic potential to design a sophisticated theranostic system is discussed in detail, along with their implications in clinical advancements which are the needs of the hour. The review concluded with the challenges, opportunities, and implications on translational potential of using gold nanoparticles in nanotheranostics.
现有的诊断和治疗方式在其准确性和理解疾病发展的几个阶段的能力方面存在重大局限性。一个优秀的治疗系统包括一个多功能的方法,在疾病的早期诊断,同时逐步治愈,使用精确的医疗方法对复杂的治疗。这些挑战可以通过纳米治疗来解决,并探索改善卫生保健的合适方法。纳米技术与治疗学相结合,作为一个非常规的平台,为开发新的战略和模式铺平了道路,从而对从急性到慢性的复杂疾病进行诊断和治疗。在金属纳米颗粒中,金纳米颗粒由于其固有的无毒性质和等离子体的特性而被广泛应用于治疗学。等离子体金属纳米颗粒独特的光学和化学特性以及治疗学已经引领了一个有希望的早期疾病检测时代,它们可以通过增强的非侵入性或微创成像对几种疾病进行实时监测。本文综述了近十年来金纳米颗粒在纳米治疗领域的应用进展。本文解释了金属纳米颗粒在纳米诊断学中的临床应用,以及未来在诊断和治疗方面的应用前景。详细讨论了金纳米颗粒的范围及其设计复杂治疗系统的现实潜力,以及它们在临床进步中的意义,这是当前的需要。综述总结了纳米金纳米颗粒在纳米治疗中的应用所面临的挑战、机遇和转化潜力。
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引用次数: 5
Application of Nanotechnology in COVID-19 Infection: Findings and Limitations 纳米技术在COVID-19感染中的应用:发现和局限性
Pub Date : 2022-11-02 DOI: 10.3390/jnt3040014
Ibrahim A. Shehu, M. Musa, A. Datta, A. Verma
There is an urgent need to address the global mortality of the COVID-19 pandemic, as it reached 6.3 million as of July 2022. As such, the experts recommended the mass diagnosis of SARS-CoV-2 infection at an early stage using nanotechnology-based sensitive diagnostic approaches. The development of nanobiosensors for Point-of-Care (POC) sampling of COVID-19 could ensure mass detection without the need for sophisticated laboratories or expert personnel. The use of Artificial Intelligence (AI) techniques for POC detection was also proposed. In addition, the utilization of various antiviral nanomaterials such as Silver Nanoparticles (AgNPs) for the development of masks for personal protection mitigates viral transmission. Nowadays, nano-assisted vaccines have been approved for emergency use, but their safety and effectiveness in the mutant strain of the SARS-CoV-2 virus remain challenging. Methodology: Updated literature was sourced from various research indexing databases such as PubMed, SCOPUS, Science Direct, Research Gate and Google Scholars. Result: We presented the concept of novel nanotechnology researched discovery, including nano-devices, electrochemical biosensing, nano-assisted vaccine, and nanomedicines, for use in recent times, which could be a formidable step for future management of COVID-19.
迫切需要解决新冠肺炎大流行的全球死亡率问题,截至2022年7月,全球死亡率已达630万。因此,专家们建议在早期阶段使用基于纳米技术的敏感诊断方法对严重急性呼吸系统综合征冠状病毒2型感染进行大规模诊断。用于新冠肺炎护理点(POC)采样的纳米生物传感器的开发可以确保在不需要复杂实验室或专家人员的情况下进行大规模检测。还提出了将人工智能(AI)技术用于POC检测。此外,利用各种抗病毒纳米材料,如银纳米粒子(AgNP)开发个人防护口罩,可以缓解病毒传播。如今,纳米辅助疫苗已被批准紧急使用,但其在严重急性呼吸系统综合征冠状病毒2型变异株中的安全性和有效性仍然具有挑战性。方法:更新的文献来源于各种研究索引数据库,如PubMed、SCOPUS、Science Direct、research Gate和Google Scholars。结果:我们提出了新的纳米技术研究发现的概念,包括纳米器件、电化学生物传感、纳米辅助疫苗和纳米药物,以供近期使用,这可能是新冠肺炎未来管理的重要一步。
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引用次数: 1
Nanostructured Silicon Enabled HR-MS for the Label-Free Detection of Biomarkers in Colorectal Cancer Plasma Small Extracellular Vesicles 纳米结构硅能HR-MS用于大肠癌癌症血浆细胞外小囊泡生物标志物的无标记检测
Pub Date : 2022-10-04 DOI: 10.3390/jnt3040013
Sanduru Thamarai Krishnan, D. Rudd, Rana Rahmani, E. E. Antunez, Rajpreet Singh Minhas, Chandra Kirana, G. Maddern, K. Fenix, E. Hauben, N. Voelcker
Despite improvements in treatment options for advanced colorectal cancer (CRC), survival outcomes are still best for patients with non-metastasised disease. Diagnostic tools to identify blood-based biomarkers and assist in CRC subtype classification could afford a means to track CRC progression and treatment response. Cancer cell-derived small extracellular vesicles (EVs) circulating in blood carry an elevated cargo of lipids and proteins that could be used as a signature of tumour suppressor/promoting events or stages leading up to and including metastasis. Here, we used pre-characterised biobanked plasma samples from surgical units, typically with a low volume (~100 µL), to generate and discover signatures of CRC-derived EVs. We employed nanostructured porous silicon (pSi) surface assisted-laser desorption/ionisation (SALDI) coupled with high-resolution mass spectrometry (HR-MS), to allow sensitive detection of low abundant analytes in plasma EVs. When applied to CRC samples, SALDI-HR-MS enabled the detection of the peptide mass fingerprint of cancer suppressor proteins, including serine/threonine phosphatases and activating-transcription factor 3. SALDI-HR-MS also allowed the detection of a spectrum of glycerophospholipids and sphingolipid signatures in metastatic CRC. We observed that lithium chloride enhanced detection sensitivity to elucidate the structure of low abundant lipids in plasma EVs. pSi SALDI can be used as an effective system for label-free and high throughput analysis of low-volume patient samples, allowing rapid and sensitive analysis for CRC classification.
尽管晚期癌症(CRC)的治疗方案有所改善,但非肿瘤患者的生存结果仍然最好。识别基于血液的生物标志物并协助CRC亚型分类的诊断工具可以提供一种跟踪CRC进展和治疗反应的方法。血液中循环的癌症细胞衍生的细胞外小泡(EVs)携带升高的脂质和蛋白质,这些脂质和蛋白质可作为导致并包括转移的肿瘤抑制/促进事件或阶段的标志。在这里,我们使用来自外科手术室的预表征生物库血浆样本,通常体积较小(约100µL),来生成和发现CRC衍生EV的特征。我们采用了纳米结构多孔硅(pSi)表面辅助激光解吸/电离(SALDI)与高分辨率质谱(HR-MS)相结合,以实现对等离子体EV中低丰度分析物的灵敏检测。当应用于CRC样品时,SALDI-HR-MS能够检测癌症抑制蛋白的肽质量指纹,包括丝氨酸/苏氨酸磷酸酶和激活转录因子3。SALDI-HR-MS还可以检测转移性CRC中的甘油磷脂和鞘脂特征。我们观察到氯化锂提高了检测灵敏度,以阐明血浆EVs中低丰度脂质的结构。pSi-SALDI可以作为一种有效的系统,用于低容量患者样本的无标记和高通量分析,允许对CRC分类进行快速灵敏的分析。
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引用次数: 1
Antibody Delivery into the Brain by Radiosensitizer Nanoparticles for Targeted Glioblastoma Therapy. 靶向胶质母细胞瘤治疗用放射增敏剂纳米颗粒将抗体输送到大脑。
Pub Date : 2022-09-30 DOI: 10.3390/jnt3040012
Omer Gal, Oshra Betzer, Liat Rousso-Noori, Tamar Sadan, Menachem Motiei, Maxim Nikitin, Dinorah Friedmann-Morvinski, Rachela Popovtzer, Aron Popovtzer

Background: Glioblastoma is the most lethal primary brain malignancy in adults. Standard of care treatment, consisting of temozolomide (TMZ) and adjuvant radiotherapy (RT), mostly does not prevent local recurrence. The inability of drugs to enter the brain, in particular antibody-based drugs and radiosensitizers, is a crucial limitation to effective glioblastoma therapy.

Methods: Here, we developed a combined strategy using radiosensitizer gold nanoparticles coated with insulin to cross the blood-brain barrier and shuttle tumor-targeting antibodies (cetuximab) into the brain.

Results: Following intravenous injection to an orthotopic glioblastoma mouse model, the nanoparticles specifically accumulated within the tumor. Combining targeted nanoparticle injection with TMZ and RT standard of care significantly inhibited tumor growth and extended survival, as compared to standard of care alone. Histological analysis of tumors showed that the combined treatment eradicated tumor cells, and decreased tumor vascularization, proliferation, and repair.

Conclusions: Our findings demonstrate radiosensitizer nanoparticles that effectively deliver antibodies into the brain, target the tumor, and effectively improve standard of care treatment outcome in glioblastoma.

背景:胶质母细胞瘤是成人最致命的原发性脑恶性肿瘤。标准的护理治疗,包括替莫唑胺(TMZ)和辅助放疗(RT),大多不能预防局部复发。药物不能进入大脑,特别是基于抗体的药物和放射增敏剂,是有效治疗胶质母细胞瘤的一个关键限制。方法:在这里,我们开发了一种联合策略,使用涂有胰岛素的放射增敏剂金纳米颗粒穿过血脑屏障,将肿瘤靶向抗体(西妥昔单抗)输送到大脑。结果:静脉注射到原位胶质母细胞瘤小鼠模型后,纳米颗粒在肿瘤内特异性积累。与单独标准治疗相比,靶向纳米颗粒注射联合TMZ和RT标准治疗可显著抑制肿瘤生长并延长生存期。肿瘤的组织学分析表明,联合治疗可以根除肿瘤细胞,减少肿瘤的血管化、增殖和修复。结论:我们的研究结果表明,放射增敏剂纳米颗粒可以有效地将抗体传递到大脑,靶向肿瘤,并有效地提高胶质母细胞瘤的护理标准治疗结果。
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引用次数: 4
Role of Nanomaterials in COVID-19 Prevention, Diagnostics, Therapeutics, and Vaccine Development 纳米材料在COVID-19预防、诊断、治疗和疫苗开发中的作用
Pub Date : 2022-09-22 DOI: 10.3390/jnt3040011
U. Patel, Kavini Rathnayake, Emily C. Hunt, Nirupama Singh
Facing the deadly pandemic caused by the SARS-CoV-2 virus all over the globe, it is crucial to devote efforts to fighting and preventing this infectious virus. Nanomaterials have gained much attention after the approval of lipid nanoparticle-based COVID-19 vaccines by the United States Food and Drug Administration (USFDA). In light of increasing demands for utilizing nanomaterials in the management of COVID-19, this comprehensive review focuses on the role of nanomaterials in the prevention, diagnostics, therapeutics, and vaccine development of COVID-19. First, we highlight the variety of nanomaterials usage in the prevention of COVID-19. We discuss the advantages of nanomaterials as well as their uses in the production of diagnostic tools and treatment methods. Finally, we review the role of nanomaterials in COVID-19 vaccine development. This review offers direction for creating products based on nanomaterials to combat COVID-19.
面对由严重急性呼吸系统综合征冠状病毒2型病毒在全球范围内引起的致命流行病,致力于抗击和预防这种传染性病毒至关重要。在美国食品和药物管理局(USFDA)批准基于脂质纳米颗粒的新冠肺炎疫苗后,纳米材料受到了广泛关注。鉴于在新冠肺炎管理中使用纳米材料的需求日益增加,本次综合综述侧重于纳米材料在新冠肺炎预防、诊断、治疗和疫苗开发中的作用。首先,我们强调了在预防新冠肺炎中使用纳米材料的多样性。我们讨论了纳米材料的优势及其在生产诊断工具和治疗方法中的应用。最后,我们回顾了纳米材料在新冠肺炎疫苗开发中的作用。这篇综述为创建基于纳米材料的产品以对抗新冠肺炎提供了方向。
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引用次数: 4
Magnetomechanical Stress-Induced Colon Cancer Cell Growth Inhibition 磁机械应力诱导的结肠癌癌症细胞生长抑制
Pub Date : 2022-08-26 DOI: 10.3390/jnt3030010
K. Spyridopoulou, Georgios Aindelis, C. Sarafidis, O. Kalogirou, K. Chlichlia
The application of magnetomechanical stress in cells using internalized magnetic nanoparticles (MNPs) actuated by low-frequency magnetic fields has been attracting considerable interest in the field of cancer research. Recent developments prove that magnetomechanical stress can inhibit cancer cells’ growth. However, the MNPs’ type and the magnetic field’s characteristics are crucial parameters. Their variability allows multiple combinations, which induce specific biological effects. We previously reported the antiproliferative effects induced in HT29 colon cancer cells by static-magnetic-field (200 mT)-actuated spherical MNPs (100 nm). Herein, we show that similar growth inhibitory effects are induced in other colon cancer cell lines. The effect of magnetomechanical stress was also examined in the growth rate of tumor spheroids. Moreover, we examined the biological mechanisms involved in the observed cell growth inhibition. Under the experimental conditions employed, no cell death was detected by PI (propidium iodide) staining analysis. Flow cytometry and Western blotting revealed that G2/M cell cycle arrest might mediate the antiproliferative effects. Furthermore, MNPs were found to locate in the lysosomes, and a decreased number of lysosomes was detected in cells that had undergone magnetomechanical stress, implying that the mechanical activation of the internalized MNPs could induce lysosome membrane disruption. Of note, the lysosomal acidic conditions were proven to affect the MNPs’ magnetic properties, evidenced by vibrating sample magnetometry (VSM) analysis. Further research on the combination of the described magnetomechanical stress with lysosome-targeting chemotherapeutic drugs could lay the groundwork for the development of novel anticancer combination treatment schemes.
在癌症研究领域,利用低频磁场驱动的内部磁性纳米颗粒(MNPs)在细胞中应用磁机械应力已经引起了相当大的兴趣。最近的发展证明磁机械应力可以抑制癌症细胞的生长。然而,MNP的类型和磁场的特性是至关重要的参数。它们的变异性允许多种组合,从而诱导特定的生物效应。我们之前报道了静止磁场(200mT)驱动的球形MNP(100nm)在HT29结肠癌癌症细胞中诱导的抗增殖作用。在此,我们发现在其他结肠癌癌症细胞系中也诱导了类似的生长抑制作用。磁机械应力对肿瘤球体生长速率的影响也得到了检验。此外,我们还研究了与观察到的细胞生长抑制有关的生物学机制。在所采用的实验条件下,通过PI(碘化丙啶)染色分析未检测到细胞死亡。流式细胞术和Western blotting显示G2/M细胞周期阻滞可能介导其抗增殖作用。此外,发现MNPs位于溶酶体中,并且在经历磁机械应力的细胞中检测到溶酶体数量减少,这意味着内化的MNPs的机械激活可以诱导溶酶体膜破坏。值得注意的是,溶酶体酸性条件已被证明会影响MNPs的磁性,振动样品磁强计(VSM)分析证明了这一点。进一步研究所描述的磁机械应力与溶酶体靶向化疗药物的结合,可以为开发新的抗癌联合治疗方案奠定基础。
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引用次数: 0
Striking Circulating Tumour Cells during Sleep 睡眠中侵袭循环肿瘤细胞
Pub Date : 2022-08-03 DOI: 10.3390/jnt3030009
S. Moghimi, S. Schwartz
Circulating tumour cells (CTCs) with stem cell-like properties and epithelial-mesenchymal transition phenotype are precursor cells responsible for dissemination and metastatic spread of cancer [...]
具有干细胞样特性和上皮-间充质转化表型的循环肿瘤细胞(CTCs)是负责癌症扩散和转移扩散的前体细胞[…]
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引用次数: 0
期刊
Journal of nanotheranostics
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