Dual‐Mode Phototherapy‐Responsive Gold‐Coated Algosomes for Enhanced Skin Cancer Therapy via Elimination of Tumor‐Resident Intracellular Bacteria

ABSTRACT Skin cancer remains a significant global health challenge, with chemotherapy often limited by suboptimal therapeutic outcomes. One of the major barriers to effective treatment is the limited penetration of chemotherapeutic agents into the tumor microenvironment, which restricts drug availability at the target site . Staphylococcus aureus infections contribute to tumor‐promoting microenvironments, chemoresistance, clustering, and invasion of melanoma cells, highlighting the need for therapeutic approaches targeting both bacterial infections and cancer. This study introduces a dual‐action nanosystem, gold‐coated algosomes (ALG/Au), synthesized from Spirulina ‐derived lipids, rich in polyunsaturated fatty acids, for combined photodynamic (PDT) and photothermal therapy (PTT) against bacteria and cancer cells. ALG/Au achieved a temperature rise up to 50°C under laser irradiation, facilitating reactive oxygen species (ROS) generation and bacterial elimination via lipid peroxidation‐mediated cell membrane damage. The system exhibited >95% inhibition of S. aureus biofilm formation, strong anti‐hemolytic activity, and excellent hemocompatibility with minimal cytotoxicity in L929 and NIH3T3 fibroblast cell lines. Additionally, ALG/Au demonstrated significant melanoma cell death in the B16 3D spheroid and S. aureus in vitro co‐culture model, underscoring its potential for targeting cancer and tumor‐residing bacteria. These findings highlight the effectiveness of ALG/Au nanoparticles in simultaneously targeting bacterial infections and cancer cells through synergistic PDT and PTT mechanisms.