Peptide-Based Double-Network Hydrogels for Melanoma Treatment and Wound Healing Promotion.

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.