Li Rui, Pavuluri Sivapriya, Bruggeman Kiara, Long Benjamin M, Parnell Andrew J, Martel Anne, Parnell Steven R, Pfeffer Frederick M, Dennison Andrew J C, Nicholas Kevin R, Barrow Colin J, Nisbet David R, Williams Richard J
Centre for Chemistry and Biotechnology, Deakin University, Waurn Ponds, Australia; Coconut Research Institute of Chinese Academy of Tropical Agricultural Sciences, Wenchang, Hainan, China.
Centre for Chemistry and Biotechnology, Deakin University, Waurn Ponds, Australia; School of Medicine, Deakin University, Waurn Ponds, VIC, Australia.
Nanomedicine. 2016 Jul;12(5):1397-407. doi: 10.1016/j.nano.2016.01.009. Epub 2016 Mar 4.
The local inflammatory environment of the cell promotes the growth of epithelial cancers. Therefore, controlling inflammation locally using a material in a sustained, non-steroidal fashion can effectively kill malignant cells without significant damage to surrounding healthy cells. A promising class of materials for such applications is the nanostructured scaffolds formed by epitope presenting minimalist self-assembled peptides; these are bioactive on a cellular length scale, while presenting as an easily handled hydrogel. Here, we show that the assembly process can distribute an anti-inflammatory polysaccharide, fucoidan, localized to the nanofibers within the scaffold to create a biomaterial for cancer therapy. We show that it supports healthy cells, while inducing apoptosis in cancerous epithelial cells, as demonstrated by the significant down-regulation of gene and protein expression pathways associated with epithelial cancer progression. Our findings highlight an innovative material approach with potential applications in local epithelial cancer immunotherapy and drug delivery.
细胞的局部炎症环境促进上皮癌的生长。因此,使用一种材料以持续、非甾体的方式局部控制炎症,可以有效杀死恶性细胞,而对周围健康细胞无显著损害。用于此类应用的一类有前景的材料是由呈现表位的极简自组装肽形成的纳米结构支架;这些材料在细胞长度尺度上具有生物活性,同时呈现为易于处理的水凝胶。在这里,我们表明组装过程可以将一种抗炎多糖——岩藻依聚糖分布到支架内的纳米纤维上,从而创建一种用于癌症治疗的生物材料。我们表明,它支持健康细胞,同时诱导癌性上皮细胞凋亡,与上皮癌进展相关的基因和蛋白质表达途径的显著下调证明了这一点。我们的研究结果突出了一种创新的材料方法,在局部上皮癌免疫治疗和药物递送方面具有潜在应用。