Phytochemical-Based Nanotherapeutics for Skin Cancer: A Critical Appraisal of Current Strategies, Challenges, and Future Perspectives.

The skin functions as the body's primary defensive barrier, safeguarding internal organs from environmental, physical, and chemical insults. Among all malignancies, skin cancer remains the most frequently diagnosed worldwide, particularly affecting individuals with lighter skin. It primarily includes basal cell carcinoma and squamous cell carcinoma, which originate from keratinocytes, and melanoma, originating from melanocytes and exhibiting greater metastatic potential. Skin cancer results from uncontrolled proliferation of abnormal cells caused by ultraviolet (UV) radiation-induced DNA damage, oxidative stress, and mutations in tumor suppressor genes. Although conventional treatments such as chemotherapy, radiotherapy, surgery, and phototherapies are widely employed, their efficacy is often limited by poor selectivity, systemic toxicity, and drug resistance. Therefore, novel, targeted, and biocompatible therapeutic strategies are urgently needed. Phytochemicals, derived from medicinal plants, have shown promising anticancer potential due to their antioxidant, anti-inflammatory, and proapoptotic activities. However, their clinical translation is restricted by poor solubility, low stability, and limited bioavailability. This review provides a distinctive perspective by integrating the therapeutic relevance of phytochemicals with advances in nanotechnology-based delivery systems for skin cancer management. It outlines disease pathophysiology, conventional therapies, and the synergistic role of nanocarriers such as liposomes, niosomes, and nanostructured lipid carriers in enhancing phytochemical delivery, improving penetration, and overcoming multidrug resistance. The review also discusses current research challenges and future directions, highlighting how phytochemical-nanotechnology hybrid systems can offer targeted, effective, and safer approaches for managing skin cancer.