从细胞到器官样体:血脑屏障技术在大脑癌药物输送建模中的演进。
From Cells to Organoids: The Evolution of Blood-Brain Barrier Technology for Modelling Drug Delivery in Brain Cancer.
发表日期:2023 Mar 15
作者:
Gonzales-Aloy E, Ahmed-Cox A, Tsoli M, Ziegler D, Kavallaris M
来源:
ADVANCED DRUG DELIVERY REVIEWS
摘要:
脑癌仍然是最致命的癌症。血脑屏障(BBB)对大多数药物具有不可渗透性,并且是一个由内皮细胞、星形细胞和血管周细胞等多种细胞类型组成的复杂三维网络。在脑癌中,BBB在肿瘤进展过程中变得不稳定,形成了血脑肿瘤屏障(BBTB)。为了推动治疗的发展,亟需具有生理学重要性的BBB体外模型。三维细胞系统作为值得重视的临床前模型,可以加速疾病研究的进展。鉴于三维细胞模型的多功能性和能力,本文就其在模拟BBB和BBTB方面的潜力进行了评估。讨论了BBB模型的技术进展、体外模拟BBTB的挑战以及这些模型在评估治疗和纳米药物递送方面的应用。预测有效的脑癌治疗的定量体外BBB模型将对加速推进新治疗方法进入临床起到不可估量的作用。版权所有©2023年Elsevier B.V.发布。
Brain cancer remains the deadliest cancer. The blood-brain barrier (BBB) is impenetrable to most drugs and is a complex 3D network of multiple cell types including endothelial cells, astrocytes, and pericytes. In brain cancers, the BBB becomes disrupted during tumor progression and forms the blood-brain tumor barrier (BBTB). To advance therapeutic development, there is a critical need for physiologically relevant BBB in vitro models. 3D cell systems are emerging as valuable preclinical models to accelerate discoveries for diseases. Given the versatility and capability of 3D cell models, their potential for modelling the BBB and BBTB is reviewed. Technological advances of BBB models and challenges of in vitro modelling the BBTB, and application of these models as tools for assessing therapeutics and nano drug delivery, are discussed. Quantitative, in vitro BBB models that are predictive of effective brain cancer therapies will be invaluable for accelerating advancing new treatments to the clinic.Copyright © 2023. Published by Elsevier B.V.