nanodecoys

纳米诱饵
  • 文章类型: Editorial
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  • 文章类型: Journal Article
    癌症转移是癌症相关死亡的主要原因,涉及肿瘤细胞和中性粒细胞之间的相互作用。在这项研究中,我们开发了活化的中性粒细胞膜涂层纳米颗粒(aNEMNP)作为纳米诱饵,以阻断中性粒细胞介导的癌症转移.通过用源自活化的嗜中性粒细胞的膜隐匿聚(乳酸)纳米颗粒来制造aNEM纳米颗粒,并继承活化的嗜中性粒细胞的功能蛋白。我们证明了aNEMNP可以干扰嗜中性粒细胞募集到原发肿瘤和转移前的壁ni,抑制中性粒细胞与肿瘤血管内皮和循环肿瘤细胞(CTC)的粘附,并在体外和体内破坏CTC-中性粒细胞簇的形成。在携带4T1的小鼠中,aNEMNP可以有效地减少乳腺癌转移到小鼠的各种器官。我们的结果表明,aNEMNP是一种有前途的纳米药物,可通过充当中性粒细胞纳米诱饵来预防或治疗癌症转移。
    Cancer metastasis is the main cause of cancer-related deaths and involves the interaction between tumor cells and neutrophils. In this study, we developed activated neutrophil membrane-coated nanoparticles (aNEM NPs) as nanodecoys to block neutrophil-mediated cancer metastasis. The aNEM NPs were fabricated by cloaking poly(lactic acid) nanoparticles with membranes derived from activated neutrophils and inherited the functional proteins of activated neutrophils. We demonstrated that aNEM NPs could interfere with the recruitment of neutrophils to the primary tumor and premetastatic niches, inhibit the adhesion of neutrophils to tumor vascular endothelium and circulating tumor cells (CTCs), and disrupt the formation of CTC-neutrophil clusters in vitro and in vivo. In 4T1-bearing mice, aNEM NPs could effectively reduce breast cancer metastasis to various organs in mice. Our results suggest that aNEM NPs are a promising nanomedicine for preventing or treating cancer metastasis by acting as neutrophil nanodecoys.
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  • 文章类型: Journal Article
    帕金森病(PD)是第二常见的神经退行性疾病,其特征是称为路易体的α-突触核蛋白(α-syn)聚集体的积累,导致黑质中多巴胺能(DA)神经元的逐渐丧失。虽然α-syn表达可以通过反义寡核苷酸(ASO)和异源双链寡核苷酸(HDO)通过侧脑室(ICV)注射减弱,安全有效地将寡核苷酸外周靶向递送到DA神经元中的挑战仍未解决。这里,我们设计了一种新的DNA/DNA双链(互补DNA,coDNA)基于α-syn-ASO序列的具有胆固醇缀合的分子(Chol-HDO(coDNA)),并评估了其沉默效率。Further,Chol-HDO@LMNPs,Chol-HDO加载,具有DSPE-PEG2000-左旋多巴修饰(L-DOPA-CECm)包被的纳米颗粒(NPs)的脑血管内皮细胞膜,被开发用于通过尾静脉注射靶向治疗PD。CECm促进NPs的血脑屏障(BBB)渗透,与从网状内皮系统摄取中逸出的胆固醇一起,以及L-DOPA脱羧成多巴胺,促进NP向PD位点进行DA神经元再生。行为测试表明,纳米诱饵改善了HDO对PD小鼠的功效。这些发现为开发加载HDO的仿生纳米诱饵以精确治疗PD提供了见解。重要性声明:α-突触核蛋白(α-syn)聚集体的积累是PD的标志。我们先前的研究设计了一种靶向人类SNCA的特异性反义寡核苷酸(ASO),但创伤性脑室内(ICV)不利于临床应用。这里,我们进一步优化ASO通过创建一个DNA/DNA双链分子与胆固醇结合,命名为Chol-HDO(coDNA),并通过使用DSPE-PEG2000和L-DOPA改造脑血管内皮细胞膜(CECm),开发了DA靶向的仿生纳米诱饵Chol-HDO@LMNPs。体内结果表明,尾静脉注射Chol-HDO@LMNPs可以靶向大脑中的DA神经元,并改善PD小鼠模型的运动缺陷。这项研究提供了一个有前途的外周递送平台L-DOPA-CECm纳米诱饵装载了一种新的Chol-HDO(coDNA)靶向PD治疗中的DA神经元。
    Parkinson\'s disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) aggregates called Lewy bodies leading to the gradual loss of dopaminergic (DA) neurons in the substantia nigra. Although α-syn expression can be attenuated by antisense oligonucleotides (ASOs) and heteroduplex oligonucleotide (HDO) by intracerebroventricular (ICV) injection, the challenge to peripheral targeted delivery of oligonucleotide safely and effectively into DA neurons remains unresolved. Here, we designed a new DNA/DNA double-stranded (complementary DNA, coDNA) molecule with cholesterol conjugation (Chol-HDO (coDNA)) based on an α-syn-ASO sequence and evaluated its silence efficiency. Further, Chol-HDO@LMNPs, Chol-HDO-loaded, cerebrovascular endothelial cell membrane with DSPE-PEG2000-levodopa modification (L-DOPA-CECm)-coated nanoparticles (NPs), were developed for the targeted treatment of PD by tail intravenous injection. CECm facilitated the blood-brain barrier (BBB) penetration of NPs, together with cholesterol escaped from reticuloendothelial system uptake, as well as L-DOPA was decarboxylated into dopamine which promoted the NPs toward the PD site for DA neuron regeneration. The behavioral tests demonstrated that the nanodecoys improved the efficacy of HDO on PD mice. These findings provide insights into the development of biomimetic nanodecoys loading HDO for precise therapy of PD. STATEMENT OF SIGNIFICANCE: The accumulation of α-synuclein (α-syn) aggregates is a hallmark of PD. Our previous study designed a specific antisense oligonucleotide (ASO) targeting human SNCA, but the traumatic intracerebroventricular (ICV) is not conducive to clinical application. Here, we further optimize the ASO by creating a DNA/DNA double-stranded molecule with cholesterol-conjugated, named Chol-HDO (coDNA), and develop a DA-targeted biomimetic nanodecoy Chol-HDO@LMNPs by engineering cerebrovascular endothelial cells membranes (CECm) with DSPE-PEG2000 and L-DOPA. The in vivo results demonstrated that tail vein injection of Chol-HDO@LMNPs could target DA neurons in the brain and ameliorate motor deficits in a PD mouse model. This investigation provides a promising peripheral delivery platform of L-DOPA-CECm nanodecoy loaded with a new Chol-HDO (coDNA) targeting DA neurons in PD therapy.
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  • 文章类型: Journal Article
    全球有超过6亿人感染了严重急性呼吸道综合症冠状病毒2(SARS-CoV-2),导致2019年冠状病毒病(COVID-19)大流行。特别是,由新出现的SARS-CoV-2变种引起的新一波COVID-19对全球人口构成新的健康风险。纳米技术已经开发出优秀的解决方案来对抗病毒大流行,例如基于ACE2的纳米诱饵,纳米抗体,纳米疫苗,和药物纳米载体。在与SARS-CoV-2变种的斗争中获得的经验教训和制定的策略也可能成为开发基于纳米技术的策略以对抗未来其他全球传染病及其变种的灵感。
    More than 600 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the pandemic of coronavirus disease 2019 (COVID-19). In particular, new waves of COVID-19 caused by emerging SARS-CoV-2 variants pose new health risks to the global population. Nanotechnology has developed excellent solutions to combat the virus pandemic, such as ACE2-based nanodecoys, nanobodies, nanovaccines, and drug nanocarriers. Lessons learned and strategies developed during this battle against SARS-CoV-2 variants may also serve as inspiration for developing nanotechnology-based strategies to combat other global infectious diseases and their variants in the future.
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  • 文章类型: Journal Article
    为各种治疗目的而设计的纳米颗粒(NPs)极大地影响了生物医学领域的科学研究,带来了一个叫做纳米医学的未来革命性领域的希望。在这一领域的一个萌芽进展是各种细胞膜结合到纳米粒子上,以发展称为“纳米诱饵”(ND)的仿生细胞,可以模仿自然细胞的功能。这种在NP上涂覆细胞膜的技术通过在身体系统内启动有效导航来增强基于纳米的技术的工作能力。由于存在多个官能部分,涂有细胞膜的纳米颗粒具有与体内复杂的生物微环境相互作用的能力。尽管最初的动机是通过涂覆红细胞膜来增加血液中的循环时间和稳定性,它进一步扩展了广泛的细胞系,如间充质干细胞,β细胞,血小板,白细胞,和癌细胞。因此,这些细胞及其带来的多功能特性在生物医学行业开辟了一个全新的领域,在那里不同的纳米颗粒配方可以以适当的剂量用于治疗多种疾病。这篇综述包括纳米诱饵在生物医学应用中的最新研究。
    Nanoparticles (NPs) designed for various theranostic purposes have hugely impacted scientific research in the field of biomedicine, bringing forth hopes of a future revolutionized area called nanomedicine. A budding advancement in this area is the conjugation of various cell membranes onto nanoparticles to develop biomimetic cells called \'Nanodecoys\' (NDs), which can imitate the functioning of natural cells. This technology of coating cell membranes on NPs has enhanced the working capabilities of nano-based techniques by initiating effective navigation within the bodily system. Due to the presence of multiple functional moieties, nanoparticles coated with cell membranes hold the ability to interact with complex biological microenvironments inside the body with ease. Although developed with the initial motive to increase the time of circulation in the bloodstream and stability by coating membranes of red blood cells, it has further outstretched a wide range of cell lines, such as mesenchymal stem cells, beta cells, thrombocytes, white blood cells, and cancer cells. Thus, these cells and the versatile properties they bring along with them open up a brand-new domain in the biomedical industry where different formulations of nanoparticles can be used in appropriate dosages to treat a plethora of diseases. This review comprises recent investigations of nanodecoys in biomedical applications.
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  • 文章类型: Journal Article
    在过去的十年中,纳米技术受到了越来越多的关注,它被用作开发更好的治疗各种疾病的模型。尽管基于纳米技术的治疗已经大大改善了治疗方案,它仍然面临着诸如流通不足,在目标区域积累不足,和不希望的毒性。在这方面,科学家们正在努力生产细胞膜伪装的纳米粒子作为一种仿生技术,用于修饰现有纳米粒子的表面,以在赋予无数所需的功能后产生显著的治疗益处。源自红细胞的膜,白细胞,癌细胞,干细胞,血小板,或细菌细胞已被用于包覆纳米颗粒表面并产生生物启发伪装的纳米颗粒。这些生物传递系统已被证明在诊断和治疗vaiorus疾病中具有潜在的应用,包括药物管理,免疫接种,免疫调节,和排毒。从成立到现在,我们提供了一个完整的描述这种先进的技术功能化纳米粒子表面。制备这些膜涂覆的纳米颗粒的方法以及它们的特性已经被彻底地讨论。在此之后,在纳米粒子的进化过程中,我们专注于来自不同细胞的细胞膜的多样性,强调这些受生物启发的隐身伪装技术如何在各种疾病状态下提高治疗效果。
    Nanotechnology has received increasing attention in the past decade and it\'s being used as a model for developing better treatments for a variety of diseases. Despite the fact that nanotechnology-based therapy has greatly improved treatment regimens, it still faces challenges such as inadequate circulation, insufficient accumulation at the target region, and undesired toxicity. In this regard, scientists are working on producing cell-membrane camouflaged nanoparticles as a biomimetic technique for modifying the surface of existing nanoparticles to produce significant therapeutic benefits following imparting myriad of desired functionalities. Membranes originating from erythrocytes, white blood cells, cancer cells, stem cells, platelets, or bacterial cells have been used to coat nanoparticle surfaces and create biologically inspired camouflaged nanoparticles. These biomemitic delivery systems have been proven to have potential applications in diagnosing and treating vaiorus diseases, including drug administration, immunisation, immunological regulation, and detoxification. From its inception to the present, we provide a complete description of this advanced technique for functionalizing nanoparticle surfaces. The method of making these membrane coated nanoparticles as well as their characterisation have been thoroughly discussed. Following that, we focused on the diversity of cell membranes derived from distinct cells in the evolution of nanoparticles, emphasising how these biologically inspired stealth - camouflaged techniques have led to increased therapeutic efficacy in a variety of disease states.
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  • 文章类型: Journal Article
    最近几年越来越强调需要开发新的活性抗病毒产品,通过使用纳米材料的人工合成工艺获得,但也来自自然矩阵。同时,先进的计算方法已经发现自己在活性疗法的再利用或减少新药发现的非常长的发展阶段的基础,这代表了一个真正的限制,尤其是在大流行的情况下。评论的第一部分集中在最具创新性的纳米材料在治疗药物领域,以及控制病毒传播的措施(即,创新的抗病毒纺织品)。评论的第二部分旨在展示计算机辅助技术如何使我们能够识别,以一种快速并因此不断更新的方式,植物衍生分子(即,萜类化合物中包含的那些)可能能够有效地与SARS-CoV-2细胞渗透途径相互作用。
    The last few years have increasingly emphasized the need to develop new active antiviral products obtained from artificial synthesis processes using nanomaterials, but also derived from natural matrices. At the same time, advanced computational approaches have found themselves fundamental in the repurposing of active therapeutics or for reducing the very long developing phases of new drugs discovery, which represents a real limitation, especially in the case of pandemics. The first part of the review is focused on the most innovative nanomaterials promising both in the field of therapeutic agents, as well as measures to control virus spread (i.e., innovative antiviral textiles). The second part of the review aims to show how computer-aided technologies can allow us to identify, in a rapid and therefore constantly updated way, plant-derived molecules (i.e., those included in terpenoids) potentially able to efficiently interact with SARS-CoV-2 cell penetration pathways.
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  • 文章类型: Journal Article
    越来越多的证据表明,在COVID-19重症病例中观察到的高炎性综合征和细胞因子风暴与疾病的不良预后密切相关。因此,靶向炎症途径似乎是对抗COVID-19的合理治疗策略。已经提出了许多抗炎剂;然而,它们中的大多数生物利用度差,不稳定性,半衰期短,以及导致脱靶效应的不良生物分布。从制药的角度来看,COVID-19炎症的含义可以作为大流行的治疗靶点和/或靶向策略。首先,可以利用药物递送系统来改善抗炎剂的性质并将其安全有效地递送至其治疗靶标。第二,可以定制药物载体以开发能够响应微环境刺激的智能递送系统,从而以选择性和特异性的方式释放抗COVID-19治疗剂。更有趣的是,一些生物系统由于其固有的抗炎效力而可以同时抑制炎症过度,并赋予其药物货物选择性地递送到受伤部位。
    Growing evidence indicates that hyperinflammatory syndrome and cytokine storm observed in COVID-19 severe cases are narrowly associated with the disease\'s poor prognosis. Therefore, targeting the inflammatory pathways seems to be a rational therapeutic strategy against COVID-19. Many anti-inflammatory agents have been proposed; however, most of them suffer from poor bioavailability, instability, short half-life, and undesirable biodistribution resulting in off-target effects. From a pharmaceutical standpoint, the implication of COVID-19 inflammation can be exploited as a therapeutic target and/or a targeting strategy against the pandemic. First, the drug delivery systems can be harnessed to improve the properties of anti-inflammatory agents and deliver them safely and efficiently to their therapeutic targets. Second, the drug carriers can be tailored to develop smart delivery systems able to respond to the microenvironmental stimuli to release the anti-COVID-19 therapeutics in a selective and specific manner. More interestingly, some biosystems can simultaneously repress the hyperinflammation due to their inherent anti-inflammatory potency and endow their drug cargo with a selective delivery to the injured sites.
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