A novel EGFR-targeted photosensitizer for the theranostics of skin cancer

The epidermal growth factor receptor (EGFR) is a critical therapeutic target implicated in the pathogenesis and progression of skin cancer, holding significant promise for enhancing precision diagnosis and treatment efficacy. In this study, we developed ICG-Z_EGFR, a novel EGFR-targeting agent engineered through conjugation of the photosensitizer indocyanine green (ICG) to an EGFR-targeted dimeric affibody (Z_EGFR) for the theranostics of EGFR-positive skin cancer. <i>In vitro</i>, ICG-Z_EGFR-mediated photothermal therapy (PTT) induced significant cell death in EGFR-positive A431 cells, while exhibiting minimal effects on EGFR-negative MLE-12 cells. Compared to free ICG, ICG-Z_EGFR enhanced tumor retention, and significantly improved tumor-targeting capability, making it advantageous for identifying EGFR-positive tumor tissues. Furthermore, ICG-Z_EGFR also exhibited excellent photothermal conversion performance <i>in vivo</i>, and effectively suppressed the growth of A431 tumors through thermal ablation. Importantly, ICG-Z_EGFR demonstrated favorable short-term safety profiles during the <i>in vivo</i> treatment assay. In conclusion, the successfully developed ICG-Z_EGFR in this study, as a novel tumor-targeted photosensitizer, innovatively breaks through the limitations of traditional single-modal treatment. This study would open up new perspectives and pathways for integrated clinical diagnosis and treatment of EGFR-positive skin cancer.