Active targeting

主动靶向
  • 文章类型: Journal Article
    尽管制药行业在药物发现和开发方面取得了所有重大进展,癌症仍然是科学界最艰巨的挑战之一。纳米技术的含义肯定已经解决了与传统抗癌模式相关的主要问题;然而,单核吞噬细胞系统(MPS)对纳米颗粒(NPs)的不希望的识别,它们在生物流体中的稳定性差,过早释放有效载荷,低生物相容性限制了其临床应用。近几十年来,基于壳聚糖(CS)的纳米递送系统(例如,聚合物NP,胶束,脂质体,树枝状聚合物,共轭,固体脂质纳米粒,等。)在改善化疗药物的药代动力学和药效学方面获得了研究人员的有希望的认可。然而,本综述的特色是主要关注并批判性地讨论各种基于CS的NPs治疗不同类型癌症的靶向潜力.根据他们的交付机制,我们将基于CS的NP分类为刺激反应性,被动,或主动靶向纳米系统。此外,各种功能化策略(例如,用聚乙二醇(PEG)接枝,疏水取代,刺激反应接头的束缚,和靶向配体的缀合)适应CS-NP的结构,用于化疗药物的靶标特异性递送也已被考虑。然而,基于CS-NP的疗法在改善治疗结果同时减轻化疗药物的脱靶效应方面具有巨大的前景。其成功的临床转化需要长期的安全性和人体临床试验.
    Despite all major advancements in drug discovery and development in the pharmaceutical industry, cancer is still one of the most arduous challenges for the scientific community. The implications of nanotechnology have certainly resolved major issues related to conventional anticancer modalities; however, the undesired recognition of nanoparticles (NPs) by the mononuclear phagocyte system (MPS), their poor stability in biological fluids, premature release of payload, and low biocompatibility have restricted their clinical translation. In recent decades, chitosan (CS)-based nanodelivery systems (eg, polymeric NPs, micelles, liposomes, dendrimers, conjugates, solid lipid nanoparticles, etc.) have attained promising recognition from researchers for improving the pharmacokinetics and pharmacodynamics of chemotherapeutics. However, the specialty of this review is to mainly focus on and critically discuss the targeting potential of various CS-based NPs for treatment of different types of cancer. Based on their delivery mechanisms, we classified CS-based NPs into stimuli-responsive, passive, or active targeting nanosystems. Moreover, various functionalization strategies (eg, grafting with polyethylene glycol (PEG), hydrophobic substitution, tethering of stimuli-responsive linkers, and conjugation of targeting ligands) adapted to the architecture of CS-NPs for target-specific delivery of chemotherapeutics have also been considered. Nevertheless, CS-NPs based therapeutics hold great promise for improving therapeutic outcomes while mitigating the off-target effects of chemotherapeutics, a long-term safety profile and clinical testing in humans are warranted for their successful clinical translation.
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  • 文章类型: Journal Article
    胰腺导管腺癌(PDAC)是最顽固的癌症之一,由于其诊断较晚,治疗反应差,和高度异构的微环境。纳米技术有可能克服一些挑战,以改善诊断和肿瘤特异性药物递送,但它们在临床环境中并不可行。该综述集中于主动靶向策略,以增强胰腺肿瘤特异性纳米粒子的摄取。此外,这篇综述强调了使用主动靶向脂质体,胶束,金纳米粒子,二氧化硅纳米颗粒,和氧化铁纳米颗粒来提高胰腺肿瘤的靶向性。使用肽将纳米颗粒主动靶向差异表达受体或PDAC肿瘤微环境(TME),抗体,小分子,多糖,荷尔蒙已经出现了。我们专注于PDAC的基于微环境的标志以及主动靶向纳米粒子克服PDAC中提出的挑战的潜力。它描述了使用纳米颗粒作为造影剂用于改善诊断和递送靶向PDAC的TME内的各个方面的化学治疗剂。此外,我们回顾了使用基于成像的技术检测到的新兴纳米造影剂,以及纳米颗粒在基于能量的PDAC治疗中的作用。本文分为:植入式材料和外科技术>手术治疗方法和药物发现中的纳米工具和技术>肿瘤疾病诊断工具的纳米医学>体内纳米诊断和成像。
    Pancreatic ductal adenocarcinoma (PDAC) is one of the most recalcitrant cancers due to its late diagnosis, poor therapeutic response, and highly heterogeneous microenvironment. Nanotechnology has the potential to overcome some of the challenges to improve diagnostics and tumor-specific drug delivery but they have not been plausibly viable in clinical settings. The review focuses on active targeting strategies to enhance pancreatic tumor-specific uptake for nanoparticles. Additionally, this review highlights using actively targeted liposomes, micelles, gold nanoparticles, silica nanoparticles, and iron oxide nanoparticles to improve pancreatic tumor targeting. Active targeting of nanoparticles toward either differentially expressed receptors or PDAC tumor microenvironment (TME) using peptides, antibodies, small molecules, polysaccharides, and hormones has been presented. We focus on microenvironment-based hallmarks of PDAC and the potential for actively targeted nanoparticles to overcome the challenges presented in PDAC. It describes the use of nanoparticles as contrast agents for improved diagnosis and the delivery of chemotherapeutic agents that target various aspects within the TME of PDAC. Additionally, we review emerging nano-contrast agents detected using imaging-based technologies and the role of nanoparticles in energy-based treatments of PDAC. This article is categorized under: Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.
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  • 文章类型: Journal Article
    当前卵巢癌(OC)研究的重点是通过最大化药物有效性来改善治疗方案。OC仍然是全球女性癌症死亡率的第五大原因。近年来,纳米技术彻底改变了药物输送系统。纳米颗粒可以用作基因治疗中的载体,或者通过限制循环中游离药物的数量来克服肿瘤中的耐药性问题,从而使不期望的副作用最小化。细胞表面受体,如人表皮生长因子2(HER2),叶酸(FA)受体,CD44(也称为归巢细胞粘附分子,HCAM),血管内皮生长因子(VEGF)在卵巢癌细胞中高表达。活性靶向纳米颗粒的产生涉及用识别细胞表面受体的配体修饰,从而促进癌细胞的内化。目前,几种聚(ADP-核糖)聚合酶(PARP)抑制剂(PARPi)用于治疗高级别浆液性卵巢癌(HGSOC)或铂敏感性复发性OC。然而,PARP耐药性和药物生物利用度差是共同的挑战,突出了发展小说的迫切需要,卵巢癌治疗的有效策略。本文综述了纳米颗粒在卵巢癌治疗中的应用。特别关注靶向方法和使用PARPi纳米载体优化治疗结果。
    The current focus of ovarian cancer (OC) research is the improvement of treatment options through maximising drug effectiveness. OC remains the fifth leading cause of cancer-induced mortality in women worldwide. In recent years, nanotechnology has revolutionised drug delivery systems. Nanoparticles may be utilised as carriers in gene therapy or to overcome the problem of drug resistance in tumours by limiting the number of free drugs in circulation and thereby minimising undesired adverse effects. Cell surface receptors, such as human epidermal growth factor 2 (HER2), folic acid (FA) receptors, CD44 (also referred to as homing cell adhesion molecule, HCAM), and vascular endothelial growth factor (VEGF) are highly expressed in ovarian cancer cells. Generation of active targeting nanoparticles involves modification with ligands that recognise cell surface receptors and thereby promote internalisation by cancer cells. Several poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are currently used for the treatment of high-grade serous ovarian carcinomas (HGSOC) or platinum-sensitive relapsed OC. However, PARP resistance and poor drug bioavailability are common challenges, highlighting the urgent need to develop novel, effective strategies for ovarian cancer treatment. This review evaluates the utility of nanoparticles in ovarian cancer therapy, with a specific focus on targeted approaches and the use of PARPi nanocarriers to optimise treatment outcomes.
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  • 文章类型: Journal Article
    炎症性肠病(IBD)是一种慢性,以肠粘膜反复发炎为特征的非特异性炎症。然而,现有的IBD治疗无效且具有严重的副作用。IBD的病因是多因素的,包括免疫,遗传,环境,饮食,和微生物因素。随着纳米技术的发展,基于特定靶向方法开发的纳米颗粒(NP)显示出巨大的潜力。纳米颗粒被定义为尺寸在1和100nm之间的颗粒。根据它们的尺寸和表面功能,NP表现出不同的性质。多种纳米颗粒类型已被用作治疗炎症性肠病(IBD)的药物载体。在实验模型中观察到令人鼓舞的结果。它们增加了药物的生物利用度,并实现了靶向药物递送,促进局部治疗,从而提高疗效。然而,从纳米医学到临床应用的转化仍然存在许多挑战,包括增强的配方和制备技术,增强药物安全性,等等。在未来,科学家和临床医生有必要合作研究疾病机制,开发新的药物输送策略,筛选新的纳米药物。然而,从纳米医学到临床应用的转化仍然存在许多挑战,包括增强的配方和制备技术,增强药物安全性,等等。在未来,科学家和临床医生有必要合作研究疾病机制,开发新的药物输送策略,筛选新的纳米药物。
    Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory condition characterized by recurring inflammation of the intestinal mucosa. However, the existing IBD treatments are ineffective and have serious side effects. The etiology of IBD is multifactorial and encompasses immune, genetic, environmental, dietary, and microbial factors. The nanoparticles (NPs) developed based on specific targeting methodologies exhibit great potential as nanotechnology advances. Nanoparticles are defined as particles between 1 and 100 nm in size. Depending on their size and surface functionality, NPs exhibit different properties. A variety of nanoparticle types have been employed as drug carriers for the treatment of inflammatory bowel disease (IBD), with encouraging outcomes observed in experimental models. They increase the bioavailability of drugs and enable targeted drug delivery, promoting localized treatment and thus enhancing efficacy. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines.
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  • 文章类型: Journal Article
    在药物开发中,活性物质在体外显示功效但缺乏在体内特异性达到其靶标的能力并不少见。因此,靶向药物递送已成为药物科学的主要焦点。自1995年Doxil®获得批准以来,脂质体已成为靶向药物递送中领先的纳米颗粒。它们的低免疫原性,通用性高,和有据可查的疗效已导致其在临床上用于治疗多种疾病。话虽如此,每种疾病都伴随着一组独特的生理条件,每个脂质体产品都必须考虑到这一点。根据应用可以采用多种不同的脂质体靶向技术。被动技术如聚乙二醇化或增强的渗透和保留作用可以改善一般的药代动力学,而诸如将靶向分子缀合到脂质体表面的活性技术可以带来甚至进一步的特异性。本文旨在总结目前靶向脂质体治疗疾病的策略。
    In drug development, it is not uncommon that an active substance exhibits efficacy in vitro but lacks the ability to specifically reach its target in vivo. As a result, targeted drug delivery has become a primary focus in the pharmaceutical sciences. Since the approval of Doxil® in 1995, liposomes have emerged as a leading nanoparticle in targeted drug delivery. Their low immunogenicity, high versatility, and well-documented efficacy have led to their clinical use against a wide variety of diseases. That being said, every disease is accompanied by a unique set of physiological conditions, and each liposomal product must be formulated with this consideration. There are a multitude of different targeting techniques for liposomes that can be employed depending on the application. Passive techniques such as PEGylation or the enhanced permeation and retention effect can improve general pharmacokinetics, while active techniques such as conjugating targeting molecules to the liposome surface may bring even further specificity. This review aims to summarize the current strategies for targeted liposomes in the treatment of diseases.
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  • 文章类型: Journal Article
    玉米醇溶蛋白是来自玉米的主要植物蛋白。近年来,玉米醇溶蛋白已被广泛用于制药,农业,食物,环境保护,和其他领域,因为它具有优异的生物相容性和生物安全性。然而,目前尚缺乏对玉米醇溶蛋白纳米递送系统的系统评价和研究。本文系统综述了玉米醇溶蛋白纳米传递系统的制备和改性方法,基于Zein的基本性质。详细论述了玉米醇溶蛋白纳米粒的制备及其影响因素,以及分析不同制备方法的优缺点,总结玉米醇溶蛋白纳米粒子的改性方法。本研究为玉米醇溶蛋白基纳米传递系统的研究提供了新的思路,促进了其应用。
    Zein is the main vegetable protein from maize. In recent years, Zein has been widely used in pharmaceutical, agriculture, food, environmental protection, and other fields because it has excellent biocompatibility and biosafety. However, there is still a lack of systematic review and research on Zein-based nano-delivery systems. This paper systematically reviews preparation and modification methods of Zein-based nano-delivery systems, based on the basic properties of Zein. It discusses the preparation of Zein nanoparticles and the influencing factors in detail, as well as analyzing the advantages and disadvantages of different preparation methods and summarizing modification methods of Zein nanoparticles. This study provides a new idea for the research of Zein-based nano-delivery system and promotes its application.
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  • 文章类型: Journal Article
    在过去的几十年里,光动力疗法(PDT)已经发展成为一种微创治疗方式,可以精确控制癌症和各种其他疾病。为了解决与PDT相关的固有挑战,研究人员一直在探索两种有希望的途径:开发通过光诱导能量转移激活的智能光敏剂,charges,或者电子转移,以及光敏键的破坏。此外,越来越重视肿瘤内光敏剂的生物正交递送或激活,使这些智能光敏系统在特定组织中的有针对性的部署和激活,从而实现高精度的PDT。这篇简明的评论强调了过去十年在光活化或生物正交光敏剂领域取得的进步,比较它们的功效,并在光动力疗法的发展中塑造未来的方向。
    Over the past few decades, photodynamic therapy (PDT) has evolved as a minimally invasive treatment modality offering precise control over cancer and various other diseases. To address inherent challenges associated with PDT, researchers have been exploring two promising avenues: the development of intelligent photosensitizers activated through light-induced energy transfers, charges, or electron transfers, and the disruption of photosensitive bonds. Moreover, there is a growing emphasis on the bioorthogonal delivery or activation of photosensitizers within tumors, enabling targeted deployment and activation of these intelligent photosensitive systems in specific tissues, thus achieving highly precise PDT. This concise review highlights advancements made over the last decade in the realm of light-activated or bioorthogonal photosensitizers, comparing their efficacy and shaping future directions in the advancement of photodynamic therapy.
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  • 文章类型: Journal Article
    细胞表面受体和相应抗体之间的特异性相互作用驱动了使用纳米颗粒系统开发靶向癌症疗法的机会。使用抗体配体设计和开发这种靶向纳米药物是具有挑战性的,因为最终的纳米缀合物的特异性取决于其组分的内聚功能。抗体缀合的纳米颗粒的多组分性质也使表征过程复杂化。不管纳米粒子的类型如何,必须进行物理化学表征,以建立坚实的知识基础并开发合适的临床前研究。对抗体缀合的纳米颗粒进行有意义的物理化学评估应包括确定抗体的数量和方向,在附件后确认抗体的完整性,并评估所获得的纳米缀合物的免疫反应性。在这次审查中,作者描述了各种技术(电泳,光谱学,比色测定,免疫测定,等。)用于分析用抗体功能化的纳米颗粒的理化性质并讨论主要结果。
    The specific interaction between cell surface receptors and corresponding antibodies has driven opportunities for developing targeted cancer therapies using nanoparticle systems. It is challenging to design and develop such targeted nanomedicines using antibody ligands, as the final nanoconjugate\'s specificity hinges on the cohesive functioning of its components. The multicomponent nature of antibody-conjugated nanoparticles also complicates the characterization process. Regardless of the type of nanoparticle, it is essential to perform physicochemical characterization to establish a solid foundation of knowledge and develop suitable preclinical studies. A meaningful physicochemical evaluation of antibody-conjugated nanoparticles should include determining the quantity and orientation of the antibodies, confirming the antibodies\' integrity following attachment, and assessing the immunoreactivity of the obtained nanoconjugates. In this review, the authors describe the various techniques (electrophoresis, spectroscopy, colorimetric assays, immunoassays, etc.) used to analyze the physicochemical properties of nanoparticles functionalized with antibodies and discuss the main results.
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  • 文章类型: Journal Article
    癌症是导致世界上所有国家死亡的严重疾病。基于纳米的药物递送方法是最好的选择,直接靶向肿瘤细胞,改善药物细胞摄取。不同类型的基于纳米颗粒的药物载体用于治疗癌症,提高癌症治疗的有效性和安全性,许多物质已被视为药物载体。最近,基于脂质的纳米颗粒(LBNP)引起了人们的极大兴趣。这些与其他聚合物交替的天然生物分子由于其两亲性质而经常在医学中再循环。脂质纳米颗粒通常提供各种益处,包括生物相容性和生物降解性。这篇综述涵盖了不同类别的LBNP,包括它们的表征和不同的合成技术。这篇综述讨论了脂质纳米颗粒技术的最重要进展及其在药物管理中的应用。此外,该综述还强调了脂质纳米颗粒在不同癌症治疗类型中的应用。
    Cancer is a severe disease that results in death in all countries of the world. A nano-based drug delivery approach is the best alternative, directly targeting cancer tumor cells with improved drug cellular uptake. Different types of nanoparticle-based drug carriers are advanced for the treatment of cancer, and to increase the therapeutic effectiveness and safety of cancer therapy, many substances have been looked into as drug carriers. Lipid-based nanoparticles (LBNPs) have significantly attracted interest recently. These natural biomolecules that alternate to other polymers are frequently recycled in medicine due to their amphipathic properties. Lipid nanoparticles typically provide a variety of benefits, including biocompatibility and biodegradability. This review covers different classes of LBNPs, including their characterization and different synthesis technologies. This review discusses the most significant advancements in lipid nanoparticle technology and their use in medicine administration. Moreover, the review also emphasized the applications of lipid nanoparticles that are used in different cancer treatment types.
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  • 文章类型: Journal Article
    纳米材料科学最近的进步为创造可靠的,有效,高度准确,和用户友好的生物医学系统。率先将天然细胞膜整合到复杂的纳米载体结构中,细胞膜伪装已经成为调节药物输送的一种变革性方法,提供最小免疫原性和主动靶向能力的好处。然而,具有这种伪装的纳米材料的效用受到诸如次优靶向精度和治疗效果不佳等挑战的限制。量身定制的细胞膜工程站在生物医学的最前沿,为纳米平台配备进行更复杂操作的能力。这篇综述首先考察了细胞膜工程中流行的方法,聚光灯策略,如直接化学修饰,脂质插入,膜杂交,代谢聚糖标记,和基因工程。在此之后,对各种纳米材料的独特属性进行了评估,提供由尖端工程细胞膜伪装驱动的实质性进步和应用的深入审查。该论述通过概述工程细胞膜伪装在纳米材料应用中的显着影响而达到顶峰,并预测其在变革性医疗技术中的开创性作用。可以设想,本文提供的见解将为工程细胞膜伪装纳米技术的创新和完善提供新的途径。
    Recent strides in nanomaterials science have paved the way for the creation of reliable, effective, highly accurate, and user-friendly biomedical systems. Pioneering the integration of natural cell membranes into sophisticated nanocarrier architectures, cell membrane camouflage has emerged as a transformative approach for regulated drug delivery, offering the benefits of minimal immunogenicity coupled with active targeting capabilities. Nevertheless, the utility of nanomaterials with such camouflage is curtailed by challenges like suboptimal targeting precision and lackluster therapeutic efficacy. Tailored cell membrane engineering stands at the forefront of biomedicine, equipping nanoplatforms with the capacity to conduct more complex operations. This review commences with an examination of prevailing methodologies in cell membrane engineering, spotlighting strategies such as direct chemical modification, lipid insertion, membrane hybridization, metabolic glycan labeling, and genetic engineering. Following this, an evaluation of the unique attributes of various nanomaterials is presented, delivering an in-depth scrutiny of the substantial advancements and applications driven by cutting-edge engineered cell membrane camouflage. The discourse culminates by recapitulating the salient influence of engineered cell membrane camouflage within nanomaterial applications and prognosticates its seminal role in transformative healthcare technologies. It is envisaged that the insights offered herein will catalyze novel avenues for the innovation and refinement of engineered cell membrane camouflaged nanotechnologies.
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