Advancing melanoma treatment with nanoparticles: from chemotherapy to combination therapies.

Nanoparticle (NPs)-based therapies have ushered in a paradigm shift in melanoma treatment, addressing key challenges in conventional chemotherapy and immunotherapy, such as drug delivery, specificity, and therapeutic efficacy. This review highlights important chemotherapies, doxorubicin, paclitaxel, cisplatin, and dacarbazine, delivered via NPs, which improve bioavailability, reduce systemic toxicity, and overcome drug resistance. Additionally, combination therapies involving chemotherapy with photothermal, photodynamic, hyperthermic, or immunotherapy treatments leverage synergies that enhance tumor regression and promote immunogenic cell death. NPs incorporating RNA interference and gene targeting have been developed to silence oncogenic pathways, enabling precision molecular targeting. Natural compounds like curcumin, resveratrol, and honokiol, delivered via NPs, show strong anticancer effects. Moreover, advanced platforms such as microneedles, hydrogels, and metal-based NPs enhance drug delivery, skin penetration, controlled release, and enable real-time monitoring with ultrasound and molecular imaging. We also discuss the potential challenges in the clinical translation of NPs-based therapies, including tumor targeting, bioavailability, multidrug resistance, immune system interactions, stability, and off-target effects. It also addresses the need for personalized, multifunctional delivery systems and strategies to overcome clinical translation barriers for effective treatment.