Department of Pharmaceutics, College of Pharmaceutical Sciences , Soochow University , Suzhou 215123 , People's Republic of China.
ACS Appl Mater Interfaces. 2018 Oct 31;10(43):36641-36651. doi: 10.1021/acsami.8b10679. Epub 2018 Oct 16.
Drug development involves various evaluation processes to ascertain drug effects and rigorous analysis of biological indicators during in vitro preclinical studies. Two-dimensional (2D) cell cultures are commonly used in numerous in vitro studies, which are poor facsimiles of the in vivo conditions. Recently, three-dimensional (3D) tumor models mimicking the tumor microenvironment and reducing the use of experimental animals have been developed generating great interest to appraise tumor response to treatment strategies in cancer therapy. In this study, silk fibroin (SF) protein and chitosan (CS), two natural biomaterials, were chosen to construct the scaffolds of 3D cell models. Human non-small cell lung cancer A549 cells in the SF/CS scaffolds were found to have a great tendency to gather and form tumor spheres. A549 cell spheres in the 3D scaffolds showed biological and morphological characteristics much closer to the in vivo tumors. Besides, the cells in 3D models displayed better invasion ability and drug resistance than 2D models. Additionally, differences in drug-resistant and immune-related protein levels were found, which indicated that 3D models might resemble the real-life situation. These findings suggested that these 3D tumor models composed of SF/CS are promising to provide a valuable biomaterial platform in the evaluation of anticancer drugs.
药物研发涉及各种评估过程，以确定药物的效果，并在体外临床前研究中对生物标志物进行严格分析。二维（2D）细胞培养常用于许多体外研究，但与体内条件相差甚远。最近，开发了三维（3D）肿瘤模型，模拟肿瘤微环境，减少实验动物的使用，这引起了人们极大的兴趣，以评估肿瘤对癌症治疗中治疗策略的反应。在这项研究中，丝素蛋白（SF）和壳聚糖（CS）这两种天然生物材料被选择来构建 3D 细胞模型的支架。在 SF/CS 支架中的人非小细胞肺癌 A549 细胞有很强的聚集和形成肿瘤球体的趋势。3D 支架中的 A549 细胞球体具有更接近体内肿瘤的生物学和形态学特征。此外，3D 模型中的细胞表现出比 2D 模型更好的侵袭能力和耐药性。此外，还发现了耐药性和免疫相关蛋白水平的差异，这表明 3D 模型可能更接近真实情况。这些发现表明，这些由 SF/CS 组成的 3D 肿瘤模型有望为评估抗癌药物提供有价值的生物材料平台。
