Multifunctional lipid nanocarriers: advancing topical skin cancer treatment

Abstract

ABSTRACT Introduction Skin cancer is among the most prevalent cancers worldwide and represents a substantial clinical and economic burden. Although topical therapy offers localized treatment and reduced systemic toxicity, its effectiveness is often limited by poor skin penetration, inadequate drug retention, and the complexity of the tumor microenvironment. These limitations have driven the development of multifunctional lipid nanocarriers that integrate therapeutic and delivery strategies within a single platform, offering opportunities to simultaneously address biological barriers and therapeutic targets and improve topical skin cancer treatment. Areas covered This review discusses advances in multifunctional lipid nanocarriers for topical skin cancer treatment, focusing on surface functionalization, stimulus-responsive systems, combination therapies, theranostic platforms, and physical delivery-assisted approaches. PubMed, Scopus, and Web of Science were searched through July 2026 without an initial date restriction. The biological rationale and potential of these strategies to improve drug delivery, tumor selectivity, and therapeutic efficacy are discussed. Expert opinion Multifunctional lipid nanocarriers offer a versatile platform for addressing limitations of conventional skin cancer therapies. Integrating complementary functionalities can enhance therapeutic performance by targeting multiple biological and delivery-related barriers. Future progress will rely on identifying combinations that provide meaningful therapeutic advantages while remaining compatible with manufacturing, regulatory, and clinical requirements. GRAPHICAL ABSTRACTThe diagram illustrates multifunctional lipid nanocarriers for topical skin cancer treatment. In the center, a cross-section of skin shows topical application targeting basal cell carcinoma, melanoma and squamous cell carcinoma. The top center depicts a nanocarrier with antibodies, peptides, polymers, imaging probes, drugs and nucleic acids. On the left, multifunctional strategies include surface functionalization, co-delivery of therapeutic agents and combination with physical methods. On the right, strategies include theranostic nanocarriers, stimuli-responsive nanocarriers and combination with physical methods. Each strategy is visually represented with corresponding icons and labels.Diagram of multifunctional lipid nanocarriers for topical skin cancer treatment.Created in BioRender. Bentley, M. (2026) https://BioRender.com/3ekyhfq.