Li Wen, Chi Naiwei, Clutter Elwin D, Zhu Bofan, Wang Rong R
Department of Chemistry, Illinois Institute of Technology, 3101 S. Dearborn St., Chicago, IL 60616, USA.
J Compos Sci. 2021 Jun;5(6). doi: 10.3390/jcs5060148. Epub 2021 Jun 2.
Fibrillar collagen is a one-dimensional biopolymer and is the most abundant structural protein in the extracellular matrix (ECM) of connective tissues. Due to the unique properties of carbon nanotubes (CNTs), considerable attention has been given to the application of CNTs in developing biocomposite materials for tissue engineering and drug delivery. When introduced to tissues, CNTs inevitably interact and integrate with collagen and impose a discernible effect on cells in the vicinity. The positive effect of the collagen-CNT (COL-CNT) matrix in tissue regeneration and the cytotoxicity of free CNTs have been investigated extensively. In this study, we aimed to examine the effect of COL-CNT on mediating the interaction between the matrix and SKOV3 ovarian cancer cells. We generated unidirectionally aligned collagen and COL-CNT nanofibrils, mimicking the structure and dimension of collagen fibrils in native tissues. AFM analysis revealed that the one-dimensional structure, high stiffness, and low adhesion of COL-CNT greatly facilitated the polarization of SKOV3 cells by regulating the β-1 integrin-mediated cell-matrix interaction, cytoskeleton rearrangement, and cell migration. Protein and gene level analyses implied that both collagen and COL-CNT matrices induced the epithelial-mesenchymal transition (EMT), and the COL-CNT matrix prompted a higher level of cell transformation. However, the induced cells expressed CD44 at a reduced level and MMP2 at an increased level, and they were responsive to the chemotherapy drug gemcitabine. The results suggested that the COL-CNT matrix induced the transdifferentiation of the epithelial cancer cells to mature, less aggressive, and less potent cells, which are inapt for tumor metastasis and chemoresistance. Thus, the presence of CNT in a collagen matrix is unlikely to cause an adverse effect on cancer patients if a controlled dose of CNT is used for drug delivery or tissue regeneration.
纤维状胶原蛋白是一种一维生物聚合物，是结缔组织细胞外基质（ECM）中含量最丰富的结构蛋白。由于碳纳米管（CNT）的独特性质，人们对其在开发用于组织工程和药物递送的生物复合材料中的应用给予了相当大的关注。当引入组织时，碳纳米管不可避免地与胶原蛋白相互作用并整合，并对附近的细胞产生明显影响。胶原蛋白 - 碳纳米管（COL - CNT）基质在组织再生中的积极作用以及游离碳纳米管的细胞毒性已得到广泛研究。在本研究中，我们旨在研究COL - CNT对介导基质与SKOV3卵巢癌细胞之间相互作用的影响。我们生成了单向排列的胶原蛋白和COL - CNT纳米纤维，模拟天然组织中胶原纤维的结构和尺寸。原子力显微镜分析表明，COL - CNT的一维结构、高刚度和低粘附性通过调节β - 1整合素介导的细胞 - 基质相互作用、细胞骨架重排和细胞迁移，极大地促进了SKOV3细胞的极化。蛋白质和基因水平分析表明，胶原蛋白和COL - CNT基质均诱导上皮 - 间质转化（EMT），并且COL - CNT基质促使更高水平的细胞转化。然而，诱导的细胞CD44表达水平降低，MMP2表达水平升高，并且它们对化疗药物吉西他滨有反应。结果表明，COL - CNT基质诱导上皮癌细胞转分化为成熟、侵袭性较低且效力较弱的细胞，这些细胞不适于肿瘤转移和化疗耐药。因此，如果将可控剂量的碳纳米管用于药物递送或组织再生，胶原蛋白基质中碳纳米管的存在不太可能对癌症患者造成不利影响。
