Three-Dimensional Silk Fibroin/Chitosan Based Microscaffold for Anticancer Drug Screening.

Three-Dimensional Silk Fibroin/Chitosan Based Microscaffold for Anticancer Drug Screening.
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用于抗癌药物筛选的三维丝素蛋白/壳聚糖微支架

DOI:
10.3389/fbioe.2022.800830
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发表时间:
2022
影响因子:
5.7
通讯作者:
Niu F
Niu F
中科院分区:
工程技术2区
文献类型:
--
作者:
Niu H;Xiao J;Lou X;Guo L;Zhang Y;Yang R;Yang H;Wang S;Niu F

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传统的单层细胞培养往往无法准确预测候选药物的抗癌活性,因为它们不能概括自然微环境。近年来,三维(3D)培养系统越来越多地应用于癌症研究和药物筛选。具有良好生物相容性的材料对于创造这样一个系统所涉及的三维肿瘤微环境至关重要。本研究以天然丝素(SF)和壳聚糖(CS)为原料,以三聚磷酸钠(TPP)和聚乙二醇单甲醚(1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide)为交联剂,制备了三维微支架。采用发射扫描电子显微镜、X射线光电子能谱、傅立叶变换红外光谱、吸水率、膨胀率等测试手段对所制得的支架材料的物化性能进行了表征。然后将癌细胞株(LoVo和MDA-MB-231)接种到支架上进行生物相容性和药物敏感性试验。扫描电子显微镜结果表明,与TPP交联支架相比,EDC交联支架具有更细小、更均匀的孔结构和更大的互联性,其吸水率约为1000%,膨胀率约为72%。这些空间结构和物理性质可以为细胞生长提供更多的黏附部位和足够的营养物质。此外,在EDC交联支架上培养的LoVo和MDA-MB-231细胞均表现出良好的黏附性和铺展性。CCK8结果显示,与2D培养相比,3D培养对化疗药物的敏感性增强,尤其是在低药物剂量(1M)的情况下。所提出的SF/CS微支架可以为抗癌药物的体外药效预测和敏感性筛选提供一个有前景的平台。
Traditional monolayer cell cultures often fail to accurately predict the anticancer activity of drug candidates, as they do not recapitulate the natural microenvironment. Recently, three-dimensional (3D) culture systems have been increasingly applied to cancer research and drug screening. Materials with good biocompatibility are crucial to create a 3D tumor microenvironment involved in such systems. In this study, natural silk fibroin (SF) and chitosan (CS) were selected as the raw materials to fabricate 3D microscaffolds; Besides, sodium tripolyphosphate (TPP), and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) were used as cross-linking agents. The physicochemical properties of obtained scaffolds were characterized with kinds of testing methods, including emission scanning electron microscopy, x-ray photoelectron spectroscopy, fourier transform infrared spectroscopy, water absorption, and swelling ratio analysis. Cancer cell lines (LoVo and MDA-MB-231) were then seeded on scaffolds for biocompatibility examination and drug sensitivity tests. SEM results showed that EDC cross-linked scaffolds had smaller and more uniform pores with great interconnection than the TPP cross-linked scaffolds, and the EDC cross-linked scaffold exhibited a water absorption ratio around 1000% and a swelling ratio of about 72%. These spatial structures and physical properties could provide more adhesion sites and sufficient nutrients for cell growth. Moreover, both LoVo and MDA-MB-231 cells cultured on the EDC cross-linked scaffold exhibited good adhesion and spreading. CCK8 results showed that increased chemotherapeutic drug sensitivity was observed in 3D culture compared with 2D culture, particularly in the condition of low drug dose (<1 M). The proposed SF/CS microscaffold can provide a promising in vitro platform for the efficacy prediction and sensitivity screening of anticancer drugs.
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