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Neutrally charged self-assembling peptide hydrogel recapitulates in vitro mechanisms of breast cancer progression
Biomaterials Advances ( IF 7.9 ) Pub Date : 2021-05-21 , DOI: 10.1016/j.msec.2021.112200
Helen C Clough 1 , Marie O'Brien 2 , Xinyi Zhu 3 , Aline F Miller 4 , Alberto Saiani 1 , Olga Tsigkou 2
Affiliation  

Self-assembling peptide hydrogels (SAPH) are a popular biomaterial due to their biocompatibility with a wide range of cell types, synthetic design, structural properties that provide a more accurate 3D microenvironment, and potential for cell- and/or drug-delivery system. Mimicking solid tumors in vitro using hydrogels is one method of testing anti-cancer drug efficacy and observing cancerous cell-ECM interactions within a 3D system. In this study, a SAPH, PeptiGel®Alpha1, was used to model in vitro the 3D breast tumor microenvironment. PeptiGel®Alpha1 is composed of entangled nanofibers with consistent diameter and mechanical properties similar to breast cancer that more accurately mimic the stiffness of breast tumor tissue than Matrigel® or collagen type I. PeptiGel®Alpha1 supported the viability and growth of the breast cancer cell lines MCF-7 and MDA-MB-231 and recapitulated key features of solid tumors such as hypoxia and invasion. MCF-7 cells in the hydrogels formed large spheroids resembling acini, while MDA-MB-231 remained dispersed. When treated with tamoxifen, PeptiGel®Alpha1 acted as a barrier, providing drug penetration geometry similar to that in vivo, providing better prediction of the drug effect. Finally, it was observed that MCF-7 cells engulfed the peptide matrix after 14 days, highlighting a potential use in drug delivery. PeptiGel®Alpha1 is a suitable platform for in vitro modeling of breast cancer.



中文翻译:

中性电荷自组装肽水凝胶概括了乳腺癌进展的体外机制

自组装肽水凝胶 (SAPH) 因其与多种细胞类型的生物相容性、合成设计、可提供更准确的 3D 微环境的结构特性以及细胞和/或药物递送系统的潜力而成为一种流行的生物材料。使用水凝胶在体外模拟实体瘤是测试抗癌药物功效和观察 3D 系统内癌细胞-ECM 相互作用的一种方法。在本研究中,使用 SAPH PeptiGel®Alpha1进行体外建模3D 乳腺肿瘤微环境。PeptiGel®Alpha1 由缠绕的纳米纤维组成,具有一致的直径和与乳腺癌相似的机械性能,比 Matrigel® 或 I 型胶原蛋白更准确地模拟了乳腺肿瘤组织的刚度。PeptiGel®Alpha1 支持乳腺癌细胞系的活力和生长MCF-7 和 MDA-MB-231 并概括了实体瘤的关键特征,例如缺氧和侵袭。水凝胶中的 MCF-7 细胞形成类似腺泡的大球体,而 MDA-MB-231 保持分散。当用他莫昔芬治疗时,PeptiGel®Alpha1 充当屏障,提供类似于体内的药物渗透几何形状,提供更好的药物效果预测。最后,观察到 MCF-7 细胞在 14 天后吞噬了肽基质,突出了在药物输送中的潜在用途。PeptiGel®Alpha1 是乳腺癌体外建模的合适平台。

更新日期:2021-06-11
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