Abstract:
Although surgery is the primary method to treat malignant melanoma, it has drawbacks such as residual tumor that could trigger cancer recurrence and wound infections that are especially difficult to heal in diabetics. In this research, we have constructed anti-cancer peptides/polyvinyl alcohol (PVA) double-network (DN) hydrogels for the treatment of melanoma. The maximum stress of the DN hydrogels is found to be larger than 2 MPa, which endows the DN hydrogels with ideal mechanical performance for therapeutic wound dressing. The peptides naphthalene-FIIIKKK (IK1) and phloretic acid-FIIIKKK (IK3) that were previously developed as effective antibacterial peptides, as well as the peptide/PVA DN hydrogels, are found to have good anti-cancer efficacy and target mouse melanoma cells B16-F10 while being nontoxic to normal cells. Further studies have revealed that IK1 and IK3 damage the tumor cell membrane and mitochondrial membrane and eventually trigger apoptosis. In the mouse melanoma model and the diabetic bacterial infection model, the DN hydrogels exhibit great anti-tumor, anti-bacterial, and wound healing promotion abilities in vivo. Because of their excellent mechanical properties, the DN hydrogels are promising soft materials for directly treating malignant melanomas as well as for preventing recurrence and bacterial infection after melanoma surgery that promote wound healing.
摘要:
虽然手术是治疗恶性黑色素瘤的主要方法,它有缺点,如残留的肿瘤,可能引发癌症复发和伤口感染,特别是难以治愈的糖尿病患者。在这项研究中,我们构建了抗癌肽/聚乙烯醇(PVA)双网络(DN)水凝胶,用于治疗黑色素瘤。发现DN水凝胶的最大应力大于2MPa,使DN水凝胶具有理想的机械性能,可用于治疗性伤口敷料。肽萘-FIIIKKK(IK1)和根草酸-FIIIKKK(IK3),以前被开发为有效的抗菌肽,以及肽/PVADN水凝胶,被发现具有良好的抗癌功效,并靶向小鼠黑色素瘤细胞B16-F10,同时对正常细胞无毒。进一步的研究表明,IK1和IK3会损伤肿瘤细胞膜和线粒体膜,并最终引发细胞凋亡。在小鼠黑色素瘤模型和糖尿病细菌感染模型中,DN水凝胶具有很强的抗肿瘤作用,抗菌,和体内伤口愈合促进能力。由于其优异的机械性能,DN水凝胶是有前途的软材料,用于直接治疗恶性黑色素瘤,以及预防黑色素瘤手术后的复发和细菌感染,促进伤口愈合。