Designed peptides are promising biomaterials for biomedical applications. The amphiphilic cationic antimicrobial peptide (AMP), AK, can self-assemble into nano-rod structures and has shown cancer cell selectivity and could therefore be a promising candidate for therapeutic delivery into cancer cells. In this paper, we investigate the selectivity of AK for cancer cell models, examining its effect on two human cancer cell lines, A431 and HCT-116. Little or no activity was observed on the control, human dermal fibroblasts (HDFs). In the cancer cell lines the peptide inhibited cellular growth through changes in mitochondrial morphology and membrane potential while remaining harmless towards HDFs. In addition, the peptide can bind to and protect nucleic acids while transporting them into both 2D cultures and 3D spheroids of cancer cells. AK showed high efficiency in delivering siRNA molecules into the centre of the spheroids. AK was also explored , using a zebrafish () development toxicity assay, showing that the peptide is safe at low doses. Finally, a high-content imaging screen, using RNA interference (RNAi) targeted towards cellular uptake, in HCT-116 cells was carried out. Our findings suggest that active cellular uptake is involved in peptide internalisation, mediated through clathrin-mediated endocytosis. These new discoveries make AK attractive for future developments in clinical and biotechnological applications.

中文翻译：

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抗菌肽 A9K 作为癌细胞中的基因传递载体

设计的肽是用于生物医学应用的有前途的生物材料。两亲性阳离子抗菌肽 (AMP) AK 可以自组装成纳米棒结构，并显示出癌细胞选择性，因此可能成为向癌细胞传递治疗的有希望的候选者。在本文中，我们研究了 AK 对癌细胞模型的选择性，检查其对两种人类癌细胞系 A431 和 HCT-116 的影响。在对照人真皮成纤维细胞 (HDF) 上观察到很少或没有活性。在癌细胞系中，该肽通过改变线粒体形态和膜电位来抑制细胞生长，同时对 HDF 无害。此外，该肽可以结合并保护核酸，同时将其转运到癌细胞的 2D 培养物和 3D 球体中。 AK 在将 siRNA 分子递送至球体中心方面表现出高效率。还使用斑马鱼 () 发育毒性测定对 AK 进行了探索，表明该肽在低剂量下是安全的。最后，在 HCT-116 细胞中使用针对细胞摄取的 RNA 干扰 (RNAi) 进行高内涵成像筛选。我们的研究结果表明，活跃的细胞摄取参与肽内化，通过网格蛋白介导的内吞作用介导。这些新发现使 AK 对临床和生物技术应用的未来发展具有吸引力。