Terpenoid-Loaded Nanoemulgels for Targeted MMP Suppression in Melanoma: Emerging Nanotherapeutic Approaches for Anti-Invasive Skin Cancer Therapy

Melanoma is an aggressive form of skin cancer characterized by rapid progression, high metastatic potential, and poor clinical prognosis in advanced stages. A key molecular event underlying melanoma invasion and metastasis is the overexpression of matrix metalloproteinases (MMP-2 and MMP-9), which facilitate extracellular matrix degradation and tumor cell dissemination. Conventional therapeutic strategies often face limitations such as drug resistance, systemic toxicity, and inadequate tumor targeting. In this context, natural bioactive compounds such as terpenoids have gained significant attention due to their intrinsic anticancer, antioxidant, and anti-inflammatory properties, particularly their ability to modulate MMP-related signaling pathways including NF-κB, PI3K/Akt, and MAPK cascades. However, their clinical application is limited by poor aqueous solubility and low bioavailability. Nanoemulgel-based drug delivery systems have emerged as a promising strategy to overcome these challenges by enhancing dermal penetration, improving physicochemical stability, and enabling controlled release of therapeutic agents. The integration of terpenoids into nanoemulgel formulations provides a synergistic platform for targeted melanoma therapy, ensuring improved localization within tumor tissues and enhanced inhibition of MMP-mediated invasion. Preclinical evidence from in vitro and in vivo studies demonstrates that terpenoid-loaded nanoemulgels significantly reduce melanoma cell proliferation, suppress angiogenesis, and induce apoptosis through modulation of oxidative stress and apoptotic signaling pathways. This review comprehensively highlights the molecular role of MMPs in melanoma progression, the therapeutic potential of terpenoids as natural MMP inhibitors, and the advantages of nanoemulgel-based delivery systems. Furthermore, it discusses recent advances in formulation strategies, nanotechnology-driven innovations, and future translational prospects. Overall, terpenoid-loaded nanoemulgels represent a promising and multifunctional nanotherapeutic approach for effective suppression of melanoma metastasis and improvement of targeted skin cancer therapy outcomes