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Biofunctional supramolecular hydrogels fabricated from a short self-assembling peptide modified with bioactive sequences for the 3D culture of breast cancer MCF-7 cells
Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2021-08-11 , DOI: 10.1016/j.bmc.2021.116345
Jyh Yea Chia 1 , Takayuki Miki 1 , Hisakazu Mihara 1 , Hiroshi Tsutsumi 1
Affiliation  

Self-assembling peptides are a type of molecule with promise as scaffold materials for cancer cell engineering. We have reported a short self-assembling peptide, (FFiK)2, that had a symmetric structure connected via a urea bond. In this study, we functionalized (FFiK)2 by conjugation with various bioactive sequences for the 3D culture of cancer cells. Four sequences, RGDS and PHSRN derived from fibronectin and AG73 and C16 derived from laminin, were selected as bioactive sequences to promote cell adhesion, proliferation or migration. (FFiK)2, and its derivatives could co-assemble into supramolecular nanofibers displaying bioactive sequences and form hydrogels. MCF-7 cells were encapsulated in functionalized peptide hydrogels without significant cytotoxicity. Encapsulated MCF-7 cells proliferated under 3D culture conditions. MCF-7 cells proliferated with spheroid formation in hydrogels that displayed RGDS or PHSRN sequences, which will be able to be applied to drug screening targeting cancer stem cells. On the other hand, since MCF-7 cells migrated in a 3D hydrogel that displayed AG73, we could construct the metastatic model of breast cancer cells, which is helpful for the elucidation of breast cancer cells and drug screening against cancer cells under metastatic state. Therefore, functionalized (FFiK)2 hydrogels with various bioactive sequences can be used to regulate cancer cell function for tumor engineering and drug screening.



中文翻译:

由生物活性序列修饰的短自组装肽制成的生物功能超分子水凝胶用于乳腺癌 MCF-7 细胞的 3D 培养

自组装肽是一种有望作为癌细胞工程支架材料的分子。我们已经报道了一种短的自组装肽 (FFiK) 2,它具有通过尿素键连接的对称结构。在这项研究中,我们通过与癌细胞 3D 培养的各种生物活性序列结合来功能化 (FFiK) 2。四个序列,源自纤连蛋白的 RGDS 和 PHSRN 以及源自层粘连蛋白的 AG73 和 C16,被选为生物活性序列,以促进细胞粘附、增殖或迁移。(FFiK) 2,及其衍生物可以共组装成具有生物活性序列的超分子纳米纤维并形成水凝胶。MCF-7 细胞被封装在功能化的肽水凝胶中,没有显着的细胞毒性。封装的 MCF-7 细胞在 3D 培养条件下增殖。MCF-7 细胞增殖并在显示 RGDS 或 PHSRN 序列的水凝胶中形成球体,这将能够应用于靶向癌症干细胞的药物筛选。另一方面,由于MCF-7细胞在显示AG73的3D水凝胶中迁移,我们可以构建乳腺癌细胞的转移模型,这有助于阐明乳腺癌细胞和针对转移状态下癌细胞的药物筛选。因此,功能化 (FFiK) 2 具有各种生物活性序列的水凝胶可用于调节癌细胞功能,用于肿瘤工程和药物筛选。

更新日期:2021-08-19
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