Drug and gene delivery

药物和基因传递
  • 文章类型: Journal Article
    噬菌体(噬菌体)代表了一种独特的病毒类别,具有选择性感染宿主细菌的显着能力,特征在于它们从蛋白质和核酸组装。利用其特殊的生物学特性和可修改的特性,噬菌体以创新的方式出现,安全,和有效的交付载体。与传统纳米载体在药物和基因递送领域相关的潜在缺点包括缺乏细胞特异性靶向,细胞毒性,并降低体内转染效率。相比之下,工程噬菌体,当被用作货物交付载体时,承诺克服这些限制,并实现增强的交付效力。这篇综述全面概述了目前噬菌体工程的策略,描述了在药物和基因递送中用作纳米载体的噬菌体的主要类型,并探讨了基于噬菌体的递送系统在疾病治疗中的应用。此外,提供了深刻的分析,批判性地研究纳米技术领域内基于噬菌体的递送系统所面临的挑战。本文的主要目的是提供理论参考,有助于有效的基于噬菌体的递送系统的合理设计和开发。
    Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from proteins and nucleic acids. Leveraging their exceptional biological properties and modifiable characteristics, phages emerge as innovative, safe, and efficient delivery vectors. The potential drawbacks associated with conventional nanocarriers in the realms of drug and gene delivery include a lack of cell-specific targeting, cytotoxicity, and diminished in vivo transfection efficiency. In contrast, engineered phages, when employed as cargo delivery vectors, hold the promise to surmount these limitations and attain enhanced delivery efficacy. This review comprehensively outlines current strategies for the engineering of phages, delineates the principal types of phages utilized as nanocarriers in drug and gene delivery, and explores the application of phage-based delivery systems in disease therapy. Additionally, an incisive analysis is provided, critically examining the challenges confronted by phage-based delivery systems within the domain of nanotechnology. The primary objective of this article is to furnish a theoretical reference that contributes to the reasoned design and development of potent phage-based delivery systems.
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  • 文章类型: Journal Article
    碳纳米点(CNDs)一种迷人的碳基纳米材料(典型尺寸2-10nm)由于其优越的光学性能,高生物相容性,和细胞穿透性,在不同的跨学科领域有巨大的应用。这里,在这篇评论中,我们首先探讨了CNDs在生物医学领域优于其他纳米材料的优势,光电子学,分析传感,和光催化域。从合成开始,表征,和纯化技术,我们甚至解决了围绕CND的基本问题,如发射起源和依赖于激发的行为。然后我们探索它们应用的最新进展,专注于生物/生物医学用途,如特定的细胞器生物成像,药物/基因递送,生物传感,和光热疗法。在光电子中,我们涵盖了基于CND的太阳能电池,钙钛矿太阳能电池,以及它们在LED和WLED中的作用。分析传感应用包括金属检测,危险化学品,和蛋白质。在催化中,我们研究在光催化中的作用,减少CO2,水分裂,立体定向合成,和污染物降解。有了这篇评论,我们打算进一步激发对CND和基于CND的复合材料的兴趣,强调它们在广泛的应用中的许多好处。
    Carbon nanodots (CNDs), a fascinating carbon-based nanomaterial (typical size 2-10 nm) owing to their superior optical properties, high biocompatibility, and cell penetrability, have tremendous applications in different interdisciplinary fields. Here, in this Review, we first explore the superiority of CNDs over other nanomaterials in the biomedical, optoelectronics, analytical sensing, and photocatalysis domains. Beginning with synthesis, characterization, and purification techniques, we even address fundamental questions surrounding CNDs such as emission origin and excitation-dependent behavior. Then we explore recent advancements in their applications, focusing on biological/biomedical uses like specific organelle bioimaging, drug/gene delivery, biosensing, and photothermal therapy. In optoelectronics, we cover CND-based solar cells, perovskite solar cells, and their role in LEDs and WLEDs. Analytical sensing applications include the detection of metals, hazardous chemicals, and proteins. In catalysis, we examine roles in photocatalysis, CO2 reduction, water splitting, stereospecific synthesis, and pollutant degradation. With this Review, we intend to further spark interest in CNDs and CND-based composites by highlighting their many benefits across a wide range of applications.
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  • 文章类型: Journal Article
    我们合成了含有共价连接的葫芦[7]脲(CB[7])的超分子聚(二硫化物)(CPS),它不仅被用作载体来递送编码不稳定的Cas9(dsCas9)的质粒DNA,但也作为宿主包括甲氧苄啶(TMP)由CB[7]部分通过超分子络合形成TMP@CPS/dsCas9。一旦质粒被CPS转染到肿瘤细胞中,多胺的存在可以竞争性地触发TMP@CPS的分解,从而从CB[7]置换和释放TMP以稳定dsCas9,其可以靶向和编辑PLK1的基因组基因座以抑制肿瘤细胞的生长。在全身施用装饰有透明质酸(HA)的TMP@CPS/dsCas9后,由于肿瘤微环境中的多胺升高,检测到PLK1的肿瘤特异性编辑,最大限度地减少健康组织和非靶向器官的脱靶编辑。由于多胺的代谢在广泛的疾病中失调,这项研究提供了一种超分子方法来精确控制特定病理背景下的CRISPR/Cas9功能.
    We synthesize supramolecular poly(disulfide) (CPS) containing covalently attached cucurbit[7]uril (CB[7]), which is exploited not only as a carrier to deliver plasmid DNA encoding destabilized Cas9 (dsCas9), but also as a host to include trimethoprim (TMP) by CB[7] moieties through the supramolecular complexation to form TMP@CPS/dsCas9. Once the plasmid is transfected into tumor cells by CPS, the presence of polyamines can competitively trigger the decomplexation of TMP@CPS, thereby displacing and releasing TMP from CB[7] to stabilize dsCas9 that can target and edit the genomic locus of PLK1 to inhibit the growth of tumor cells. Following the systemic administration of TMP@CPS/dsCas9 decorated with hyaluronic acid (HA), tumor-specific editing of PLK1 is detected due to the elevated polyamines in tumor microenvironment, greatly minimizing off-target editing in healthy tissues and non-targeted organs. As the metabolism of polyamines is dysregulated in a wide range of disorders, this study offers a supramolecular approach to precisely control CRISPR/Cas9 functions under particular pathological contexts.
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  • 文章类型: Journal Article
    纳米技术是一个跨学科领域,已成为癌症治疗的热门话题。金属有机骨架(MOFs)是由有机连接剂和金属阳离子组成的多孔材料和混合复合材料。尽管MOFs在其他领域得到了广泛的应用,最近的研究揭示了MOFs用于癌症治疗的潜力.高表面积和孔隙率,显著的药物负载和包封效率是在药物递送中使用MOF的益处之一。MOF可以递送具有肿瘤细胞选择性靶向的基因/药物,这可以通过用配体官能化实现。包括碳点和金纳米颗粒的光敏剂和光响应性纳米结构可以装载在MOF中/上,以引起光疗介导的肿瘤消融。免疫原性细胞死亡诱导和细胞毒性CD8+和CD4+T细胞的浸润增加可以通过MOF平台在提供肿瘤细胞的免疫治疗中加速。响应于pH的刺激响应性MOF平台,氧化还原,酶和离子可以加速肿瘤部位治疗剂的释放。此外,MOF纳米复合材料可以修饰配体和绿色聚合物,以提高其对癌症治疗的选择性和生物相容性。应用MOFs检测癌症相关生物标志物可参与患者的早期诊断。
    The nanotechnology is an interdisciplinary field that has become a hot topic in cancer therapy. Metal-organic frameworks (MOFs) are porous materials and hybrid composites consisted of organic linkers and metal cations. Despite the wide application of MOFs in other fields, the potential of MOFs for purpose of cancer therapy has been revealed by the recent studies. High surface area and porosity, significant drug loading and encapsulation efficiency are among the benefits of using MOFs in drug delivery. MOFs can deliver genes/drugs with selective targeting of tumor cells that can be achieved through functionalization with ligands. The photosensitizers and photo-responsive nanostructures including carbon dots and gold nanoparticles can be loaded in/on MOFs to cause phototherapy-mediated tumor ablation. The immunogenic cell death induction and increased infiltration of cytotoxic CD8+ and CD4+ T cells can be accelerated by MOF platforms in providing immunotherapy of tumor cells. The stimuli-responsive MOF platforms responsive to pH, redox, enzyme and ion can accelerate release of therapeutics in tumor site. Moreover, MOF nanocomposites can be modified ligands and green polymers to improve their selectivity and biocompatibility for cancer therapy. The application of MOFs for the detection of cancer-related biomarkers can participate in the early diagnosis of patients.
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  • 文章类型: Journal Article
    乳腺癌是女性最常见的恶性肿瘤。基于壳聚糖(CS)的纳米颗粒已被引入乳腺癌治疗中,以增加药物和基因向肿瘤部位的靶向递送。CS纳米结构通过增强货物(药物和基因)的靶向递送及其在肿瘤细胞中的积累来抑制肿瘤发生。肿瘤细胞通过内吞作用内化基于CS的纳米颗粒。此外,壳聚糖纳米载体也可以诱导光疗介导的肿瘤消融。智能和多功能类型的CS纳米粒子,包括pH-,光和氧化还原响应纳米粒子,可用于提高乳腺癌切除的潜力。此外,CS纳米粒子对免疫治疗的加速,并且有可能开发可用于抑制肿瘤发生的CS纳米颗粒水凝胶。
    Breast cancer is the most common and malignant tumor among women. Chitosan (CS)-based nanoparticles have been introduced into breast cancer therapy as a way to increase the targeted delivery of drugs and genes to the tumor site. CS nanostructures suppress tumorigenesis by enhancing both the targeted delivery of cargo (drug and gene) and its accumulation in tumor cells. The tumor cells internalize CS-based nanoparticles through endocytosis. Moreover, chitosan nanocarriers can also induce phototherapy-mediated tumor ablation. Smart and multifunctional types of CS nanoparticles, including pH-, light- and redox-responsive nanoparticles, can be used to improve the potential for breast cancer removal. In addition, the acceleration of immunotherapy by CS nanoparticles has also been achieved, and there is potential to develop CS-nanoparticle hydrogels that can be used to suppress tumorigenesis.
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  • 文章类型: Journal Article
    肿瘤学的最新进展涉及多功能纳米结构的创建。将纳米粒子整合到癌症治疗领域带来了变革的转变,彻底改变了解决肿瘤消除中现有挑战和局限性的方法。这在对抗抵抗运动的出现时尤其关键,这大大削弱了化疗和放疗等治疗方法的有效性。GO是一种碳衍生的纳米粒子,它越来越多地在不同的领域找到效用,尤其是在生物医学领域。GO纳米结构的利用在肿瘤学领域有希望,能够将药物和遗传物质精确运输到目标地点。GO纳米材料提供了增强药物的药代动力学行为和生物利用度的机会,这些纳米载体增加了药物在肿瘤位置的积累。GO纳米结构封装了基因,保护它们免受降解并促进它们在癌细胞中的吸收,从而促进有效的基因沉默。GO促进光疗的能力已导致在减少肿瘤进展方面的显著进步。通过PDT和PTT的组合,GO纳米材料具有减少肿瘤发生的能力。GO纳米材料有可能触发细胞和先天免疫,使他们成为疫苗开发的有希望的竞争者。此外,响应特定刺激的GO纳米颗粒类型已被应用于癌症根除,以及用于癌症检测和生物标志物诊断的目的。胞吞作用是GO纳米材料内化的机制。鉴于这些优势,强烈建议使用GO纳米材料消除肿瘤。
    The latest advancements in oncology involves the creation of multifunctional nanostructures. The integration of nanoparticles into the realm of cancer therapy has brought about a transformative shift, revolutionizing the approach to addressing existing challenges and limitations in tumor elimination. This is particularly crucial in combating the emergence of resistance, which has significantly undermined the effectiveness of treatments like chemotherapy and radiotherapy. GO stands as a carbon-derived nanoparticle that is increasingly finding utility across diverse domains, notably in the realm of biomedicine. The utilization of GO nanostructures holds promise in the arena of oncology, enabling precise transportation of drugs and genetic material to targeted sites. GO nanomaterials offer the opportunity to enhance the pharmacokinetic behavior and bioavailability of drugs, with documented instances of these nanocarriers elevating drug accumulation at the tumor location. The GO nanostructures encapsulate genes, shielding them from degradation and facilitating their uptake within cancer cells, thereby promoting efficient gene silencing. The capability of GO to facilitate phototherapy has led to notable advancements in reducing tumor progression. By PDT and PTT combination, GO nanomaterials hold the capacity to diminish tumorigenesis. GO nanomaterials have the potential to trigger both cellular and innate immunity, making them promising contenders for vaccine development. Additionally, types of GO nanoparticles that respond to specific stimuli have been applied in cancer eradication, as well as for the purpose of cancer detection and biomarker diagnosis. Endocytosis serves as the mechanism through which GO nanomaterials are internalized. Given these advantages, the utilization of GO nanomaterials for tumor elimination comes highly recommended.
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  • 文章类型: Journal Article
    对纳米材料在癌症治疗领域的应用的兴趣是,包括化学抗性在内的常规疗法的缺点,纳米技术可以解决肿瘤细胞的放射性抵抗和缺乏特异性靶向的问题。环糊精(CD)是两亲性环状寡糖,可以以α-,β-和γ-CD,它们可以从天然来源合成。由于这些纳米复合物在改善当前生物活性物质和癌症治疗剂的溶解度和生物利用度方面的益处,CD在癌症中的应用显示出增加的趋势。CD广泛用于癌症治疗中的药物和基因递送,通过将这些治疗剂靶向递送到目标部位,它们提高了抗增殖和抗癌的潜力。使用基于CD的纳米结构可以改善治疗剂的血液循环时间和肿瘤部位积累。更重要的是,CD的刺激响应类型,包括pH-,氧化还原和光敏型可以加速肿瘤部位生物活性化合物的释放。有趣的是,CD能够介导光热和光动力影响,损害癌症的肿瘤发生,增强细胞死亡和改善对化疗的反应。在提高CD的靶向能力方面,它们与配体的表面官能化已经进行。此外,CDs可以用绿色产品如壳聚糖和岩藻聚糖改性,它们可以嵌入绿色纳米结构中以抑制肿瘤发生。CD内化进入肿瘤细胞可以通过内吞作用发生,这可以是clethrin-,窝或受体介导的内吞作用。此外,CD是生物成像中很有前途的候选者,癌细胞和细胞器成像以及分离肿瘤细胞。在癌症治疗中使用CD的主要好处包括药物和基因的持续和低释放,有针对性的交付,货物的生物响应释放,易于表面功能化和与其他纳米结构的络合。CD在克服耐药性方面的应用需要更多的研究。
    The interest towards application of nanomaterials in field of cancer therapy is that the drawbacks of conventional therapies including chemoresistance, radio-resistance and lack of specific targeting of tumor cells can be solved by nanotechnology. Cyclodextrins (CDs) are amphiphilic cyclic oligosaccharides that can be present in three forms of α-, β- and γ-CDs, and they can be synthesized from natural sources. The application of CDs in cancer shows an increasing trend due to benefits of these nanocomplexes in improving solubility and bioavailability of current bioactives and therapeutics for cancer. CDs are widely utilized in delivery of drugs and genes in cancer therapy, and by targeted delivery of these therapeutics into target site, they improve anti-proliferative and anti-cancer potential. The blood circulation time and tumor site accumulation of therapeutics can be improved using CD-based nanostructures. More importantly, the stimuli-responsive types of CDs including pH-, redox- and light-sensitive types can accelerate release of bioactive compound at tumor site. Interestingly, the CDs are able to mediate photothermal and photodynamic impact in impairing tumorigenesis in cancer, enhancing cell death and improving response to chemotherapy. In improving the targeting ability of CDs, their surface functionalization with ligands has been conducted. Moreover, CDs can be modified with green products such as chitosan and fucoidan, and they can be embedded in green-based nanostructures to suppress tumorigenesis. The internalization of CDs into tumor cells can occur through endocytosis and this can be clethrin-, caveolae- or receptor-mediated endocytosis. Furthermore, CDs are promising candidates in bioimaging, cancer cell and organelle imaging as well as isolating tumor cells. The main benefits of using CDs in cancer therapy including sustained and low release of drugs and genes, targeted delivery, bioresponsive release of cargo, ease of surface functionalization and complexation with other nanostructures. The application of CDs in overcoming drug resistance requires more investigation.
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  • 文章类型: Journal Article
    纳米生物技术领域的建设性成就及其转化为临床课程,导致人们越来越关注评估其用于治疗疾病的用途,尤其是癌症。骨肉瘤(OS)是儿童和青春期男性和女性的原发性骨恶性肿瘤之一。像其他类型的癌症一样,遗传和表观遗传突变是OS进展的原因,我们采用了包括化疗和手术在内的几种常规疗法.然而,OS患者的生存率仍然很低,该领域的新疗法有限.本综述的目的是提供OS治疗中使用的纳米结构的总结。通过纳米平台的药物和基因递送已经导致用于肿瘤细胞抑制的治疗剂的积累。此外,通过纳米结构共同递送基因和药物用于OS抑制以促进免疫疗法。由于肿瘤细胞具有不同的特征,如酸性pH,刺激响应性纳米粒子已被开发为适当的目标OS。此外,纳米平台可用于生物传感和提供光疗以抑制OS。此外,用配体对纳米颗粒进行表面修饰可以增加其对OS细胞的特异性和选择性。当前发现的临床翻译表明,纳米平台在延缓肿瘤生长和提高OS患者生存率方面是有效的。
    Constructive achievements in the field of nanobiotechnology and their translation into clinical course have led to increasing attention towards evaluation of their use for treatment of diseases, especially cancer. Osteosarcoma (OS) is one of the primary bone malignancies that affects both males and females in childhood and adolescence. Like other types of cancers, genetic and epigenetic mutations account for OS progression and several conventional therapies including chemotherapy and surgery are employed. However, survival rate of OS patients remains low and new therapies in this field are limited. The purpose of the current review is to provide a summary of nanostructures used in OS treatment. Drug and gene delivery by nanoplatforms have resulted in an accumulation of therapeutic agents for tumor cell suppression. Furthermore, co-delivery of genes and drugs by nanostructures are utilized in OS suppression to boost immunotherapy. Since tumor cells have distinct features such as acidic pH, stimuli-responsive nanoparticles have been developed to appropriately target OS. Besides, nanoplatforms can be used for biosensing and providing phototherapy to suppress OS. Furthermore, surface modification of nanoparticles with ligands can increase their specificity and selectivity towards OS cells. Clinical translation of current findings suggests that nanoplatforms have been effective in retarding tumor growth and improving survival of OS patients.
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  • 文章类型: Journal Article
    化疗是治疗癌症的首选,并且总是优于其他方法,例如放射和手术,但它从未满足患者对安全有效药物的需求。因此,现在需要在癌症治疗方面取得新的进展,以减少癌症患者化疗带来的副作用和负担。现在正在积极探索使用纳米技术的靶向治疗,因为它们可以有效地将治疗剂输送到肿瘤细胞而不影响正常细胞。树枝状聚合物是有前途的纳米载体,具有独特的理化性质,在癌症治疗研究中受到了相当大的关注。这部分是由于其表面上的许多官能团。在这次审查中,我们讨论了不同类型的树枝状聚合物作为癌症治疗递送系统的进展,专注于挑战,机遇,和聚合物分子的功能。本文还回顾了树枝状聚合物在通过内吞作用进入细胞中的各种作用,以及癌症中的分子和炎症途径。此外,各种基于树枝状聚合物的药物递送(例如,pH响应,酶反应性,氧化还原响应,热响应,等。)和脂质-,氨基酸-,用于基因递送的基于聚合物和纳米颗粒的修饰,以及与树枝状聚合物共同递送癌症治疗中的药物和基因,被呈现。最后,讨论了生物安全问题和阻碍树枝状聚合物从研究到临床过渡的问题,以阐明其临床应用。
    Chemotherapy is the first choice in the treatment of cancer and is always preferred to other approaches such as radiation and surgery, but it has never met the need of patients for a safe and effective drug. Therefore, new advances in cancer treatment are now needed to reduce the side effects and burdens associated with chemotherapy for cancer patients. Targeted treatment using nanotechnology are now being actively explored as they could effectively deliver therapeutic agents to tumor cells without affecting normal cells. Dendrimers are promising nanocarriers with distinct physiochemical properties that have received considerable attention in cancer therapy studies, which is partly due to the numerous functional groups on their surface. In this review, we discuss the progress of different types of dendrimers as delivery systems in cancer therapy, focusing on the challenges, opportunities, and functionalities of the polymeric molecules. The paper also reviews the various role of dendrimers in their entry into cells via endocytosis, as well as the molecular and inflammatory pathways in cancer. In addition, various dendrimers-based drug delivery (e.g., pH-responsive, enzyme-responsive, redox-responsive, thermo-responsive, etc.) and lipid-, amino acid-, polymer- and nanoparticle-based modifications for gene delivery, as well as co-delivery of drugs and genes in cancer therapy with dendrimers, are presented. Finally, biosafety concerns and issues hindering the transition of dendrimers from research to the clinic are discussed to shed light on their clinical applications.
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  • 文章类型: Journal Article
    RNA结合蛋白(RBP)在RNA指导过程中发挥着非常关键的作用。这些RBPs的非典型表达影响RNA代谢的许多步骤,主要改变它的表达。RNA结合蛋白的表达改变和功能障碍导致癌症进展和其他疾病。我们列举了各种可用的干预措施,和最近的发现集中在靶向RBP用于癌症治疗和诊断。治疗,致敏,化学预防,基因介导,和病毒介导的干预研究,以治疗和诊断癌症。被动和主动靶向脂质纳米粒子的应用,聚合物纳米颗粒,基于病毒的粒子,讨论了基于疫苗的免疫疗法,用于递送针对癌症的治疗剂。我们还讨论了用于在作用部位实现递送的纳米颗粒的制剂方面和正在进行的靶向RBP的临床试验。
    RNA binding proteins (RBPs) enact a very crucial part in the RNA directive processes. Atypical expression of these RBPs affects many steps of RNA metabolism, majorly altering its expression. Altered expression and dysfunction of RNA binding proteins lead to cancer progression and other diseases. We enumerate various available interventions, and recent findings focused on targeting RBPs for cancer therapy and diagnosis. The treatment, sensitization, chemoprevention, gene-mediated, and virus mediated interventions were studied to treat and diagnose cancer. The application of passively and actively targeted lipidic nanoparticles, polymeric nanoparticles, virus-based particles, and vaccine-based immunotherapy for the delivery of therapeutic agent/s against cancer are discussed. We also discuss the formulation aspect of nanoparticles for achieving delivery at the site of action and ongoing clinical trials targeting RBPs.
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