Tumor Microenvironment Based on Extracellular Matrix Hydrogels for On-Chip Drug Screening

Biosensors Pub Date : 2024-09-05 DOI:10.3390/bios14090429
Xiaoyan Liu, Jinxiong Cheng, Yingcan Zhao
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Abstract

Recent advances in three-dimensional (3D) culturing and nanotechnology offer promising pathways to overcome the limitations of drug screening, particularly for tumors like neuroblastoma. In this study, we develop a high-throughput microfluidic chip that integrates a concentration gradient generator (CGG) with a 3D co-culture system, constructing the vascularized microenvironment in tumors by co-culturing neuroblastoma (SY5Y cell line) and human brain microvascular endothelial cells (HBMVECs) within a decellularized extracellular matrix (dECM) hydrogels. The automated platform enhances the simulation of the tumor microenvironment and allows for the precise control of the concentrations of nanomedicines, which is crucial for evaluating therapeutic efficacy. The findings demonstrate that the high-throughput platform can significantly accelerate drug discovery. It efficiently screens and analyzes drug interactions in a biologically relevant setting, potentially revolutionizing the drug screening process.
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基于细胞外基质水凝胶的肿瘤微环境用于片上药物筛选
三维(3D)培养和纳米技术的最新进展为克服药物筛选,尤其是神经母细胞瘤等肿瘤药物筛选的局限性提供了前景广阔的途径。在这项研究中,我们开发了一种高通量微流控芯片,它将浓度梯度发生器(CGG)与三维共培养系统集成在一起,通过在脱细胞细胞外基质(dECM)水凝胶中共培养神经母细胞瘤(SY5Y 细胞系)和人脑微血管内皮细胞(HBMVECs)来构建肿瘤的血管化微环境。该自动化平台增强了对肿瘤微环境的模拟,并能精确控制纳米药物的浓度,这对评估疗效至关重要。研究结果表明,高通量平台可以大大加快药物发现的速度。它能在生物相关的环境中有效地筛选和分析药物相互作用,有可能彻底改变药物筛选过程。
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