小鸡绒毛膜:用于筛选肿瘤抗血管生成疗法纳米制剂的宝贵三维体内模型。

Anna Senrung, Tanya Tripathi, Divya Janjua, Sunita Kumari Yadav, Arun Chhokar, Nikita Aggarwal, Joni Yadav, Apoorva Chaudhary, Udit Joshi, Pallavi Sethi, Alok Chandra Bharti
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引用次数: 0

摘要

药物发现是一个漫长的过程。从确定先导化合物到批准临床应用,需要经过一系列劳动密集型的体外、体内临床前筛选和临床试验。在成千上万种经过筛选的药物中,只有少数能获准进行临床试验。此外,这些获批药物在临床用药剂量下往往会因全身毒性和并发症而停药。为了克服这些局限性,纳米制剂已成为在肿瘤内以治疗浓度安全有效地递送药物的最受欢迎的策略。最重要的是,采用适当可变的临床前模型对于候选药物或其制剂的治疗评估至关重要。回顾过去 10 年有关抗血管生成纳米制剂的文献,可以发现临床前模型的类型有限,主要是二维(2D)单层细胞培养和小鼠模型,是药物吸收、毒性和效率研究的主流。最重要的是,小鼠模型成本高、耗时长,而且需要专业的操作技能。本综述重点介绍了如何利用鸡绒毛膜(CAM)这一历史悠久、定义明确的血管生成模型,在经济的框架内研究抗血管生成化合物和纳米制剂。在实际应用方面,我们对 CAM 模型进行了评估,以证明抗血管生成化合物的筛选,以及肿瘤细胞可以通过招募宿主内皮细胞和其他细胞成分,植入发育中的 CAM 上,以生长异种移植物。此外,通过证明静脉注射氧化铁纳米粒子(IONPs)可在高血管性异种移植物中被动积聚并表现出细胞内和细胞外分区积聚,也加强了利用 CAM 肿瘤异种移植物模型评估纳米粒子分布的可能性。最后,还强调了使用 CAM 作为测试潜在疗法的实验模型的伦理考虑因素、益处和缺点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chick chorioallantoic membrane: a valuable 3D in vivo model for screening nanoformulations for tumor antiangiogenic therapeutics.

Drug discovery is an extensive process. From identifying lead compounds to approval for clinical application, it goes through a sequence of labor-intensive in vitro, in vivo preclinical screening and clinical trials. Among thousands of drugs screened only a few get approval for clinical trials. Furthermore, these approved drugs are often discontinued due to systemic toxicity and comorbidity at clinically administered dosages. To overcome these limitations, nanoformulations have emerged as the most sought-after strategy to safely and effectively deliver drugs within tumors at therapeutic concentrations. Most importantly, the employment of suitably variable preclinical models is considered highly critical for the therapeutic evaluation of candidate drugs or their formulations. A review of literature from the past 10 years on antiangiogenic nanoformulations shows the employment of limited types of preclinical models mainly the 2-dimensional (2D) monolayer cell culture and murine models as the mainstay for drug uptake, toxicity and efficiency studies. To top it all, murine models are highly expensive, time-consuming and require expertise in handling them. The current review highlights the utilization of the age-old chicken chorioallantoic membrane (CAM), a well-defined angiogenic model in the investigation of antiangiogenic compounds and nanoformulations in an economic framework. For practical applicability, we have evaluated the CAM model to demonstrate the screening of antiangiogenic compounds and that tumor cells can be implanted onto developing CAM for growing xenografts by recruiting host endothelial and other cellular components. In addition, the exploitation of CAM tumor xenograft models for the evaluation of nanoparticle distribution has also been reinforced by demonstrating that intravenously administered iron oxide nanoparticles (IONPs) passively accumulate and exhibit intracellular as well as extracellular compartment accumulation in highly vascular xenografts. Finally, the ethical considerations, benefits, and drawbacks, of using CAM as an experimental model for testing potential therapeutics are also highlighted.

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