Molecular Determinants of Skin Cancer and Lipid Nanocarriers as Precision Drug-Delivery Platforms

The skin, the largest organ of the human body, acts as a crucial protective barrier against environmental threats. Skin cancers such as melanoma, basal cell carcinoma, and squamous cell carcinoma are linked to recurrent gene changes in BRAF, NRAS, KIT, KRAS, TP53, ARID1A, ARID2, and NOTCH1. These genetic alterations promote cancer growth by disrupting key cellular signaling pathways. For example, BRAF mutations like V600E and NRAS mutations like Q61R activate the MAPK/ERK pathway, aiding melanoma development. TP53 mutations, often due to UV exposure, are common in cutaneous squamous cell carcinoma. Traditional chemotherapy can destroy cancer cells but also damages healthy tissues. Lipid nanotechnology offers a promising alternative, enabling better drug delivery in skin cancer. Liposomes, ethosomes, and lipid nanoparticles (LNPs) are small enough to penetrate skin barriers, enhance drug bioavailability, and target delivery specifically. LNPs can carry anticancer drugs and biological molecules like genes, antibodies, DNA, and RNA, while increasing stability and cell uptake. This review explores the causes and genetic factors of skin cancer and recent progress in lipid-based nanocarriers for treatment. It also examines their potential to boost therapy effectiveness and improve patient outcomes.