Photo-immunotherapeutic PDA-Ce6-R837 nanoparticles enhance the induction of immunogenic responses in melanoma cells

Abstract

Melanoma is a highly aggressive malignancy characterized by limited immunogenicity and pronounced immune evasion, which represent significant obstacles to effective therapeutic intervention. Building on our previously developed multifunctional PDA-Ce6-R837 nanoparticles (NPs), which have demonstrated favorable antitumor efficacy in squamous cell carcinoma (SCC) models, the present study shifts focus toward elucidating their underlying photo-immunological mechanisms in melanoma cells. Here, we investigate their antitumor and immunoregulatory effects in melanoma cell models. In vitro studies demonstrated the efficient internalization of PDA-Ce6-R837 NPs by SK-Mel-28 and A375 cells, which was accompanied by pronounced photothermal and photodynamic responses. Functional assays revealed that this treatment markedly suppressed cell migration and invasion and, under dual-wavelength laser irradiation, significantly induced apoptosis while promoting key hallmarks of immunogenic cell death (ICD), including the translocation of calreticulin (CRT) and the extracellular release of adenosine triphosphate (ATP) and high-mobility group box 1 (HMGB1). In coculture systems, treatment with R837 alone promoted the maturation of bone marrow-derived dendritic cells (BMDCs), whereas laser activation of PDA-Ce6-R837 NPs enhanced BMDC maturation, as evidenced by further upregulation of CD80/CD86 expression and increased IL-12p70 production. Collectively, these findings demonstrate that PDA-Ce6-R837 NPs combine direct cytotoxic effects with immune stimulation in melanoma phototherapy, offering experimental evidence to support the development of phototherapy-based immunotherapeutic strategies for melanoma.