Engineered maleoyl-chitosan grafted with oligopeptides nanogels with dual-mode mobility toward melanoma therapy

Melanoma is a particularly aggressive form of skin cancer, and existing conventional chemotherapies, such as dacarbazine (DTIC), tend to have poor selectivity and limited therapeutic efficacy. As a result, the development of advanced nanocarrier systems that combine magnetic guidance with enzyme-driven motion to enhance drug distribution and stability is a promising approach to address these challenges. In this study, self-assembled magnetic nanogels with dual-mode mobility composed of maleoyl-chitosan (MAC) grafted with oligopeptides containing leucine (Leu) and N-Carbobenzyloxy-lysine (Cbz-Lys) moieties via N-carboxyanhydride ring-opening polymerization and magnetic nanoparticles (MNPs) immobilized with glucose oxidase (GOx) were prepared and utilized as therapeutic systems for the delivery of DTIC. These nanosystems were characterized in terms of their structure, morphology, and colloidal stability. The GOx-MNP core-based nanogels had remanent magnetization for external magnetic guidance, as well as enzymatic propulsion in the presence of glucose, as confirmed by particle tracking assay. Mean square displacement (MSD) profiles revealed superdiffusive motion for all systems, which can potentially facilitate tissue penetration. The highest Cbz-Lys content increased the velocity up to 8.9 μm/s, attributed to the concentration gradient and surface interactions. In vivo assays confirmed good hemocompatibility and biocompatibility without adverse effects on the liver or kidney. DTIC-loaded nanogels demonstrated strong cytotoxicity against cancer cells while reducing toxicity to fibroblasts. Overall, this study presents a proof-of-concept platform that utilizes glyco-oligopeptide nanogels combined with magnetic guidance and enzymatic-driven motility, aiming to improve drug penetration and delivery in melanoma therapy.