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) doublenetwork (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.

Developing conductive hydrogels for biomedical applications

“…Moreover, to deal with the mechanical brittle nature of conductive polymers, double networks (DN) can be introduced into conductive hydrogels, which is achieved by adopting a non-conductive matrix as the first supporting network and the conductive polymer as the second network. 51 The interpenetration networks can impart the conductive hydrogels with greater mechanical performance.…”

Multifunctional Therapeutic Nanodiamond Hydrogels for Infected-Wound Healing and Cancer Therapy

“…Researchers have recently developed various hydrogels − and nanoplatforms − that can simultaneously inhibit tumor growth and promote wound healing. However, limited biocompatibility, inevitable particle aggregation, rapid leakage of encapsulated drugs, and uneven distribution still limit the application of nanoparticles for wound treatment.…”

“…For the treatment of malignant tumors, injectable hydrogels can be used as carriers of therapeutic reagents and tissue repair scaffolds. Furthermore, they can be used in a minimally invasive manner without surgical intervention. , Therefore, injectable hydrogels are potential treatment platforms for antitumor, hemostasis, sterilization, and wound healing. , …”

Photofabrication of fluorescent nanospheres from de novo designed peptides, and their enzyme-responsive dissociation in living cells

“…13–16 Peptide assemblies are ordinarily governed by a combination of noncovalent and covalent interactions, encompassing hydrogen bonds, 17 π–π stacking, 18 hydrophobic interactions, 19,20 coulombic forces, 21,22 disulfide S–S bonds, 23,24 l -phenylalanine polymerization, dityrosine crosslinking, 25–27 and so on, which could drive peptide self-assembly processes, stabilize secondary or tertiary structures, and establish conjugation patterns even at the protein level. Tremendous efforts have been made to exploit de novo designed peptides and mimic bioactive assemblies, however, the function-oriented synthesis is still limited by many influencing factors of pH environment, 28–30 working temperature, 31–33 ionic strength, 34,35 hydrophilic/hydrophobic properties, 36,37 pre-assembly method, 38,39 host–guest modeling, 40,41 spacer occupation, 42,43 and so on.…”