Harnessing Lipid-Based Nanocarriers for Skin Cancer Therapy: A Comprehensive Review of Drug Delivery, Gene-Based...

Skin cancer, including melanoma and non-melanoma subtypes, remains a major global health challenge with steadily rising incidence rates. Although conventional treatment modalities such as surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy have improved patient outcomes, their clinical effectiveness is frequently limited by poor cutaneous penetration, systemic toxicity, non-specific drug distribution, and the emergence of drug resistance. In this context, lipid-based nanocarriers (LBNCs) have emerged as a promising strategy to address these therapeutic limitations. This comprehensive review highlights recent advances in LBNCs, including liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), transferosomes, ethosomes, and invasomes, for the management of skin cancer. The review discusses the physicochemical properties and mechanisms by which these nanocarriers enhance topical and transdermal drug delivery by overcoming the stratum corneum barrier through hydration, lipid fluidization, and follicular targeting. Furthermore, the role of LBNCs in achieving tumor-specific accumulation via passive targeting through the enhanced permeability and retention (EPR) effect, as well as active targeting using ligandfunctionalized systems, is critically examined. Particular emphasis is placed on lipid nanoparticles as nonviral vectors for gene therapy, enabling the efficient delivery of nucleic acids such as siRNA, mRNA, and CRISPR/Cas9 components to modulate oncogenic pathways. Recent preclinical and clinical developments, including personalized mRNA-based cancer vaccines, are summarized to demonstrate the translational potential of LBNCs. Overall, this review underscores the versatility of lipid-based nanocarriers as multifunctional, biocompatible, and patient-friendly platforms, offering new opportunities for precise, effective, and personalized skin cancer therapy.