Recent Advances in Nanomedicine-Enhanced Photodynamic Therapy in Cutaneous Oncology: Melanoma-Dominant Evidence for Immunogenic Cell Death and Photoimmunotherapy

Although photodynamic therapy (PDT) is a recognised treatment for the premalignant keratinocytic lesion actinic keratosis (AK) and selected superficial skin cancers, poor photosensitiser delivery, restricted light penetration and tumour hypoxia can significantly restrict its effectiveness. Recent advances in nanomedicine are extending PDT past improved transport of the photosensitiser. These approaches can also control tumour accumulation, intracellular localisation and the generation of reactive oxygen species. The degree of tumour cell damage is not the only outcome that can be influenced by these features. They can also influence tumour-cell death and immunogenic cell death (ICD)-associated danger signalling and, in selected preclinical systems, support antigen presentation and T-cell activation. Nanomedicine-enhanced PDT has increasingly been integrated with immune-checkpoint blockade and immune adjuvants in melanoma models. In selected preclinical melanoma models, these combinations have improved local tumour control and produced antitumour effects at untreated distant or metastatic sites; functional immune memory has been demonstrated only in a smaller subset of studies using tumour-rechallenge models. Nanotechnology may further address the practical limitations of conventional PDT while improving treatment precision. This is shown by skin-directed delivery, oxygen-generating systems and theranostic platforms. However, immune-related evidence remains predominantly preclinical and melanoma-based, whereas human nanomedicine evidence in AK and basal cell carcinoma (BCC) largely concerns nanoformulation-assisted PDT rather than immune modulation. Overall, the field is progressing from nanoparticle-assisted phototoxicity towards integrated photoimmunotherapy. Treatment delivery, tumour destruction and immune activation are increasingly being considered together. Together, these findings support the continued development of nanomedicine-enhanced PDT across cutaneous oncology, while emphasising that the most advanced immune and photoimmunotherapy evidence currently remains melanoma-based.