Carboxymethylcellulose/Hyaluronic Acid Hybrid Nanoconjugates: Toward Multifunctional Platforms for Melanoma Skin Cancer Theranostics

Melanoma remains one of the most aggressive forms of skin cancer, characterized by high metastatic potential and risks of tissue trauma and post-surgical recurrence, with limited therapeutic options currently available. While conventional monotherapies often fail to provide comprehensive and efficient treatment, nanoparticle-functionalized hydrogel platforms have emerged as promising multifunctional systems for localized combination cancer therapy, capable of integrating multiple therapeutic modalities, such as chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT), tissue recovery support, antibacterial activity, and image-guided treatment into a single biomaterial. This review examines stimulus-responsive hydrogels based on the anionic polysaccharides carboxymethylcellulose (CMC) and hyaluronic acid (HA), conjugated with nanoparticles for melanoma theranostic applications. It evaluates their design, synergistic mechanisms, and therapeutic potential. It considers how combining CMC and HA overcomes the limitations of individual polymers, such as poor mechanical integrity and rapid degradation, and enhances key functionalities, particularly cell targeting and specificity. It also analyzes how incorporating functional nanoparticles can enable on-demand drug release, diagnostic imaging, immune microenvironment remodeling, and combined phototherapy (PTT/PDT). While HA-based nanotheranostic systems are widely documented, the potential of CMC in melanoma treatment remains largely untapped, despite its proven success in tissue engineering and wound management. Most significantly, the literature currently lacks any bio-nanohybrid platform that integrates CMC and HA, driven by functional hybrid nanoparticles, for targeted melanoma therapy. By identifying this critical gap, this review proposes new research avenues for designing these unified, multifunctional platforms as a highly promising strategy for cutaneous melanoma management.