An EGFR-directed photoimmunotheranostic conjugate enables tumor-specific imaging and potent synergistic antitumor activity.

Resistance to anti-epidermal growth factor receptor (EGFR) antibodies represents a major bottleneck in treating EGFR-overexpressing tumors such as skin cancer. While conventional photodynamic therapy offers a promising alternative, its efficacy is often constrained by poor targeting and limited tissue penetration. To address this, we developed a photoimmunodiagnostic-therapeutic conjugate (PPC) based on panitumumab and the near-infrared photosensitizer IR808, aiming to integrate tumor-specific targeting, real-time fluorescence imaging, and synergistic therapy. In vivo experiments demonstrated that PPC selectively accumulates at tumor sites, enabling sustained near-infrared fluorescence imaging. Following light exposure, it significantly suppressed tumor growth through the synergistic effects of photodynamic killing and immune activation without inducing notable systemic toxicity. This study offers a novel integrated diagnostic-therapeutic strategy for EGFR-positive malignancies, highlighting the photobiological mechanisms underlying its antitumor effects and demonstrating the potential of antibody-photosensitizer conjugates in photomedicine.