Targeted delivery

有针对性的交付
  • 文章类型: Journal Article
    外泌体,作为一类与各类肿瘤生物学行为密切相关的细胞外小囊泡,目前在癌症诊断和治疗方面引起了研究的关注。关于癌症诊断,其膜结构的稳定性和在体液中的广泛分布使外泌体成为有希望的生物标志物。预计基于外泌体的液体活检将成为未来肿瘤诊断的重要工具。对于癌症治疗,外泌体,作为细胞之间的“黄金传播者”,可以设计成提供不同的药物,旨在实现低毒、低免疫原性的靶向递送。与外泌体内容物相关的信号通路也可以用于针对肿瘤的更安全和更有效的免疫疗法。外泌体来自广泛的来源,在不同的癌症治疗中表现出不同的生物学特性和临床应用优势。在这次审查中,我们分析了在癌症诊断和治疗中具有巨大潜力和广阔前景的外泌体的主要来源。此外,我们比较了它们的治疗优势,为外泌体的临床应用提供新思路。
    Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the \"golden communicators\" between cells, can be designed to deliver different drugs, aiming to achieve low-toxicity and low-immunogenicity targeted delivery. Signaling pathways related to exosome contents can also be used for safer and more effective immunotherapy against tumors. Exosomes are derived from a wide range of sources, and exhibit different biological characteristics as well as clinical application advantages in different cancer therapies. In this review, we analyzed the main sources of exosomes that have great potential and broad prospects in cancer diagnosis and therapy. Moreover, we compared their therapeutic advantages, providing new ideas for the clinical application of exosomes.
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  • 文章类型: Journal Article
    信使RNA(mRNA)已成为一种有前途的治疗分子,在治疗中枢神经系统疾病中具有许多临床应用。肿瘤,COVID-19和其他疾病。mRNA治疗必须封装到安全,稳定,和有效的运载工具,以保护货物免于降解并防止免疫原性。外泌体由于其良好的生物相容性,在mRNA递送中获得了越来越多的关注,低免疫原性,小尺寸,穿过生理屏障的独特能力,和细胞特异性的向性。此外,这些外泌体可以被工程化以利用天然载体靶向特定的细胞或组织。这种靶向方法将增强mRNAs的功效并减少其副作用。然而,必须解决一些困难,例如缺乏一致且可靠的外泌体纯化方法以及将大mRNA有效封装到外泌体中。本文概述了当前在细胞来源的囊泡介导的mRNA递送及其生物医学应用方面的突破。
    Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity. Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism. Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs. However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed. This article outlines current breakthroughs in cell-derived vesicle-mediated mRNA delivery and its biomedical applications.
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  • 文章类型: Journal Article
    中枢神经系统(CNS)肿瘤是严重的难治性疾病,预后不良。特别是恶性胶质母细胞瘤和脑转移患者。目前,许多研究已经探索了细菌和肠道菌群在肿瘤发展和治疗中的潜在作用。细菌可以穿透血脑屏障(BBB),靶向肿瘤核心的缺氧微环境,从而消除肿瘤并激活先天和适应性免疫反应,使它们成为中枢神经系统肿瘤的有希望的治疗剂。此外,工程细菌和衍生物,如细菌膜蛋白和细菌孢子,还可以作为靶向给药的良好候选载体。此外,肠道菌群可以通过“肠-脑轴”调节中枢神经系统肿瘤代谢并影响免疫微环境。因此,细菌抗肿瘤治疗,工程化细菌靶向药物递送,和肠道菌群的干预为CNS肿瘤的治疗提供了治疗方式。在本文中,我们对细菌治疗中枢神经系统肿瘤的机制和治疗实践进行了全面回顾,并讨论了该领域未来潜在的研究方向.
    Tumors of the central nervous system (CNS) are severe and refractory diseases with poor prognosis, especially for patients with malignant glioblastoma and brain metastases. Currently, numerous studies have explored the potential role of bacteria and intestinal flora in tumor development and treatment. Bacteria can penetrate the blood-brain barrier (BBB), targeting the hypoxic microenvironment at the core of tumors, thereby eliminating tumors and activating both the innate and adaptive immune responses, rendering them promising therapeutic agents for CNS tumors. In addition, engineered bacteria and derivatives, such as bacterial membrane proteins and bacterial spores, can also be used as good candidate carriers for targeted drug delivery. Moreover, the intestinal flora can regulate CNS tumor metabolism and influence the immune microenvironment through the \"gut-brain axis\". Therefore, bacterial anti-tumor therapy, engineered bacterial targeted drug delivery, and intervention of the intestinal flora provide therapeutic modalities for the treatment of CNS tumors. In this paper, we performed a comprehensive review of the mechanisms and therapeutic practices of bacterial therapy for CNS tumors and discussed potential future research directions in this field.
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  • 文章类型: Journal Article
    纳米工程已经成为癌症治疗的一种渐进方法,提供精确和靶向的治疗剂递送,同时降低整体毒性。这篇学术文章探讨了纳米工程的创新策略和进步,弥合了临床实践和癌症治疗领域研究之间的差距。各种纳米工程平台,如纳米颗粒,脂质体,和树枝状聚合物被仔细审查它们封装药物的能力,增强药物功效,并增强药代动力学。此外,这篇文章调查了推动纳米工程疗法进步和增强的研究突破,包括生物标志物的识别,建立临床前模型,和生物材料的进步,所有这些对于将实验室研究结果转化为实际的医疗干预措施都是必不可少的。此外,纳米技术与成像模式的整合,放大了癌症的检测,治疗监测,和反应评估,被彻底检查。最后,纳米工程的障碍和未来方向,包括与可扩展性相关的监管挑战和问题,被检查。这强调了促进各种实体之间合作的重要性,以便有效地将纳米工程干预措施转化为增强的癌症治疗和患者管理。
    Nanoengineering has emerged as a progressive method in cancer treatment, offering precise and targeted delivery of therapeutic agents while concurrently reducing overall toxicity. This scholarly article delves into the innovative strategies and advancements in nanoengineering that bridge the gap between clinical practice and research in the field of cancer treatment. Various nanoengineered platforms such as nanoparticles, liposomes, and dendrimers are scrutinized for their capacity to encapsulate drugs, augment drug efficacy, and enhance pharmacokinetics. Moreover, the article investigates research breakthroughs that drive the progression and enhancement of nanoengineered remedies, encompassing the identification of biomarkers, establishment of preclinical models, and advancement of biomaterials, all of which are imperative for translating laboratory findings into practical medical interventions. Furthermore, the integration of nanotechnology with imaging modalities, which amplify cancer detection, treatment monitoring, and response assessment, is thoroughly examined. Finally, the obstacles and prospective directions in nanoengineering, including regulatory challenges and issues related to scalability, are examined. This underscores the significance of fostering collaboration among various entities in order to efficiently translate nanoengineered interventions into enhanced cancer therapies and patient management.
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  • 文章类型: Journal Article
    根据世界卫生组织(WHO)的数据,癌症被认为是全球死亡的主要原因之一,和新的治疗方法,特别是改进的新型癌症治疗方案,需求很高。考虑到许多化疗药物往往具有较差的药代动力学特征,包括快速清除和有限的现场积累,与肿瘤归巢肽(THP)功能化磁性纳米颗粒联合使用的方法可能会带来显著的改善.这一领域越来越多的论文证实了这一点,表明磁性纳米颗粒的靶肽功能化改善了它们的渗透性能,并确保了肿瘤特异性结合,导致临床反应增加。这篇综述旨在强调THP与磁性载体结合在各个领域的潜在应用,包括药物经济学的观点。
    According to data from the World Health Organization (WHO), cancer is considered to be one of the leading causes of death worldwide, and new therapeutic approaches, especially improved novel cancer treatment regimens, are in high demand. Considering that many chemotherapeutic drugs tend to have poor pharmacokinetic profiles, including rapid clearance and limited on-site accumulation, a combined approach with tumor-homing peptide (THP)-functionalized magnetic nanoparticles could lead to remarkable improvements. This is confirmed by an increasing number of papers in this field, showing that the on-target peptide functionalization of magnetic nanoparticles improves their penetration properties and ensures tumor-specific binding, which results in an increased clinical response. This review aims to highlight the potential applications of THPs in combination with magnetic carriers across various fields, including a pharmacoeconomic perspective.
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  • 文章类型: Journal Article
    信使核糖核酸(mRNA)已成为一种有前途的分子预防和治疗方法,为医疗保健开辟了新途径。虽然使用输送系统,特别是脂质纳米颗粒(LNP),大大提高了mRNA的效率和稳定性,mRNA倾向于在肝脏中积累,并且在静脉注射后几乎不穿透生理屏障以到达靶位点。因此,旨在将mRNA引导至特定组织和细胞的靶向策略的合理设计仍然是mRNA治疗中的巨大挑战.高通量筛选(HTS)是一种尖端的靶向技术,能够合成用于大规模实验的化合物文库,以验证mRNA递送系统的效率。在这次审查中,我们首先概述了传统的低吞吐量靶向策略。然后是用于mRNA靶向递送的HTS技术的最新进展,包括优化大型运载工具的结构和开发大型表面配体,并对HTS技术在肝外系统疾病中的应用进行了综述。此外,我们说明了靶向mRNA递送的给药途径的选择。最后,提出了该领域的挑战和解决这些挑战的潜在解决方案,为mRNA靶向治疗的未来发展提供见解。
    Messenger ribonucleic acid (mRNA) has emerged as a promising molecular preventive and therapeutic approach that opens new avenues for healthcare. Although the use of delivery systems, especially lipid nanoparticles (LNPs), greatly improves the efficiency and stability of mRNA, mRNA tends to accumulate in the liver and hardly penetrates physiological barriers to reach the target site after intravenous injection. Hence, the rational design of targeting strategies aimed at directing mRNA to specific tissues and cells remains an enormous challenge in mRNA therapy. High-throughput screening (HTS) is a cutting-edge targeted technique capable of synthesizing chemical compound libraries for the large-scale experiments to validate the efficiency of mRNA delivery system. In this review, we firstly provide an overview of conventional low-throughput targeting strategies. Then the latest advancements in HTS techniques for mRNA targeted delivery, encompassing optimizing structures of large-scale delivery vehicles and developing large-scale surface ligands, as well as the applications of HTS techniques in extrahepatic systemic diseases are comprehensively summarized. Moreover, we illustrate the selection of administration routes for targeted mRNA delivery. Finally, challenges in the field and potential solutions to tackle them are proposed, offering insights for future development toward mRNA targeted therapy.
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  • 文章类型: Journal Article
    纳米颗粒已显示出通过增强的渗透性和保留效应用于肿瘤靶向递送的巨大潜力。然而,肿瘤机械微环境,以致密的细胞外基质(ECM)为特征,高肿瘤硬度和固体应力,导致只有0.7%的给药剂量积累在实体瘤中,甚至更少(〜0.0014%)达到肿瘤细胞,限制纳米颗粒的治疗功效。此外,肿瘤机械微环境可以调节肿瘤细胞的干性,促进肿瘤侵袭,转移和降低治疗疗效。在这次审查中,介绍了机械的检测方法。调节机械微环境的策略,包括通过物理,化学和生物方法,ECM形成的破坏,耗尽或抑制癌症相关的成纤维细胞,然后总结。最后,讨论了机械调节策略的进一步临床应用以增强纳米药物的治疗效果的前景和挑战。本综述可为纳米颗粒的合理设计和临床应用提供指导。
    Nanoparticles have shown great potential for tumor targeting delivery via enhanced permeability and retention effect. However, the tumor mechanical microenvironment, characterized by dense extracellular matrix (ECM), high tumor stiffness and solid stress, leads to only 0.7% of administered dose accumulating in solid tumors and even fewer (∼0.0014%) reaching tumor cells, limiting the therapeutic efficacy of nanoparticles. Furthermore, the tumor mechanical microenvironment can regulate tumor cell stemness, promote tumor invasion, metastasis and reduce treatment efficacy. In this review, methods detecting the mechanical are introduced. Strategies for modulating the mechanical microenvironment including elimination of dense ECM by physical, chemical and biological methods, disruption of ECM formation, depletion or inhibition of cancer-associated fibroblasts, are then summarized. Finally, prospects and challenges for further clinical applications of mechano-modulating strategies to enhance the therapeutic efficacy of nanomedicines are discussed. This review may provide guidance for the rational design and application of nanoparticles in clinical settings.
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  • 文章类型: Journal Article
    目前的免疫疗法具有意想不到的严重副作用和治疗阻力,并没有导致黑色素瘤患者的预期结果,需要发现更有效的药物。来自眼镜蛇毒液的细胞毒素(CTX)已被确定具有良好的细胞溶解活性和抗肿瘤功效,被认为是一种有前途的新型抗癌剂。然而,具有优异阴离子磷脂酰丝氨酸脂质结合能力的两亲性CTX也可能损害正常细胞。
    我们开发了具有高CTX载量(CTX@PSL)的pH响应性脂质体,用于肿瘤微环境中药物的靶向酸性刺激释放。形态学,尺寸,zeta电位,药物释放动力学,并对保存稳定性进行了表征。细胞摄取,促凋亡作用,使用MTT法和流式细胞术评估细胞毒性。最后,使用体内成像系统系统评估CTX@PSL的组织分布和抗肿瘤作用.
    CTX@PSL表现出高药物包封率,药物装载,稳定性,和在酸性条件下的快速释放曲线。这些纳米粒子,不规则球形,尺寸小,可以有效地在肿瘤部位积聚(比游离CTX高六倍),并迅速内化到癌细胞中(细胞摄取效率高2.5倍)。CTX@PSL显示出明显更强的细胞毒性(IC50为0.25μg/mL),并且比其他制剂中的细胞凋亡增加(凋亡率71.78±1.70%)。CTX@PSL的抑瘤效果明显优于游离CTX或常规脂质体(抑瘤率79.78±5.93%)。
    我们的结果表明,CTX@PSL改善了肿瘤位点的积累和细胞内的摄取,从而持续和靶向地释放CTX。通过结合CTX和刺激响应纳米技术的优势,新型CTX@PSL纳米制剂是癌症治疗的有希望的治疗候选药物.
    UNASSIGNED: Current immunotherapies with unexpected severe side effects and treatment resistance have not resulted in the desired outcomes for patients with melanoma, and there is a need to discover more effective medications. Cytotoxin (CTX) from Cobra Venom has been established to have favorable cytolytic activity and antitumor efficacy and is regarded as a promising novel anticancer agent. However, amphiphilic CTX with excellent anionic phosphatidylserine lipid-binding ability may also damage normal cells.
    UNASSIGNED: We developed pH-responsive liposomes with a high CTX load (CTX@PSL) for targeted acidic-stimuli release of drugs in the tumor microenvironment. The morphology, size, zeta potential, drug-release kinetics, and preservation stability were characterized. Cell uptake, apoptosis-promoting effects, and cytotoxicity were assessed using MTT assay and flow cytometry. Finally, the tissue distribution and antitumor effects of CTX@PSL were systematically assessed using an in vivo imaging system.
    UNASSIGNED: CTX@PSL exhibited high drug entrapment efficiency, drug loading, stability, and a rapid release profile under acidic conditions. These nanoparticles, irregularly spherical in shape and small in size, can effectively accumulate at tumor sites (six times higher than free CTX) and are rapidly internalized into cancer cells (2.5-fold higher cell uptake efficiency). CTX@PSL displayed significantly stronger cytotoxicity (IC50 0.25 μg/mL) and increased apoptosis in than the other formulations (apoptosis rate 71.78±1.70%). CTX@PSL showed considerably better tumor inhibition efficacy than free CTX or conventional liposomes (tumor inhibition rate 79.78±5.93%).
    UNASSIGNED: Our results suggest that CTX@PSL improves tumor-site accumulation and intracellular uptake for sustained and targeted CTX release. By combining the advantages of CTX and stimuli-responsive nanotechnology, the novel CTX@PSL nanoformulation is a promising therapeutic candidate for cancer treatment.
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  • 文章类型: Journal Article
    寻常痤疮是一种以毛囊为中心的慢性炎症性皮肤病,使毛囊靶向递送抗痤疮药物成为痤疮治疗的有希望的选择。然而,目前的研究只集中在传递到健康的毛囊,这与寻常痤疮中病理堵塞的毛囊本质上是不同的。
    通过湿介质研磨或高压均质化制备了具有不同粒径的壬二酸(AZA)微/纳米晶体。进行了AZA微/纳米晶体向健康毛囊递送的实验,使用和不使用物理增强技术。更重要的是,它创新地设计了一个实验,这可以揭示AZA微/纳米晶体穿透构建的堵塞毛囊的能力。使用脂多糖刺激的RAW264.7细胞模型和粉刺杆菌模型在体外评估AZA微/纳米晶体的抗炎和抗菌作用。最后,在体内比较了AZA微/纳米晶体和商业产品的抗痤疮作用和皮肤安全性。
    与商业产品相比,200nm和500nm的AZA微/纳米晶体表现出增加的靶向毛囊的能力。在AZA微/纳米晶体和超声的组合组中,穿透毛囊的能力进一步显着增强(ER值高达9.6)。然而,朝向堵塞的毛囊,AZA微/纳米晶体不能轻易地通过自身渗入。仅在1%水杨酸的帮助下,AZA微/纳米晶体具有很好的穿透堵塞的毛囊的潜力。还表明AZA微/纳米晶体通过抑制促炎因子和痤疮杆菌而具有抗炎和抗菌作用。与商业产品相比,AZA微/纳米晶体和超声的组合在皮肤安全性和体内抗痤疮治疗效果上都表现出明显的优势。
    毛囊靶向递送AZA微/纳米晶体在促进寻常痤疮治疗方面提供了令人满意的替代方案。
    UNASSIGNED: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris.
    UNASSIGNED: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo.
    UNASSIGNED: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy.
    UNASSIGNED: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.
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  • 文章类型: Journal Article
    癌症是女性第二大致命疾病。近年来,利用基于碳量子点(CQDs)的策略作为靶向药物递送系统对推进和改善癌症治疗产生了重大影响.这项研究的重点是纳米载体的开发,基于CQDs,用于提高米托蒽醌(MTX)的治疗效率。因此,通过水热法合成了N掺杂的CQDs。净化后,MTX被加载到CQD,导致尺寸从36.78±0.9nm增加到157.8±12.18nm,理想的药物包封率为97%。药物释放调查显示pH依赖性改善,在48小时后,从pH7.4的8%到pH5.2的11%。基于对MCF-7乳腺癌细胞处理5小时后的甲基噻唑基二苯基-四唑溴化物(MTT)结果,N掺杂CQD对癌细胞无显著影响,而N掺杂的CQD-MTX复合物在0.5至0.8μM的浓度下达到一半最大抑制浓度(IC50)。因此,新开发的药物递送复合物能够对MCF-7细胞提供相当相同的影响,作为免费的MTX,然而,通过控制和靶向药物释放来改善药物的药代动力学,由于分布和吸收参数的变化。
    Cancer is the second most fatal disease among women. In recent years, utilizing strategies based on carbon quantum dots (CQDs) as targeted drug delivery systems has had a significant impact on advancing and improving cancer treatment. This study is focused on the development of a nanocarrier, based on CQDs, for improving the therapeutic efficiency of mitoxantrone (MTX). Hence, the N-doped CQDs were synthesized by a hydrothermal method. Following its purification, MTX was loaded to the CQD, resulting in an increase in the size from 36.78 ± 0.9 nm to 157.8 ± 12.18 nm, with an ideal drug entrapment efficiency of 97 %. Drug release investigation showed a pH-dependent improvement, from 8 % at pH 7.4 to 11 % at pH 5.2 after 48 h. Based on the Methylthiazolyldiphenyl-tetrazolium bromide (MTT) results after 5 h of treatment on MCF-7 breast cancer cells, the N-doped CQD showed no significant effect on the cancer cells, whereas a half maximal Inhibitory Concentration (IC50) was achieved with the N-doped CQD-MTX complex at a concentration between 0.5 to 0.8 μM. Therefore, the newly developed drug delivery complex was capable of providing a rather identical influence on MCF-7 cells, as the free MTX, however, improving the pharmacokinetic of the drug by its controlled and on-target drug release, due to an alteration in distribution and absorption parameters.
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