Implantable micro-scale LED device guided photodynamic therapy to potentiate antitumor immunity with mild visible light

Background: Photodynamic therapy (PDT) is a promising strategy to promote antitumor immunity by inducing immunogenic cell death (ICD) in tumor cells. However, practical PDT uses an intense visible light owing to the shallow penetration depth of the light, resulting in immunosuppression at the tumor tissues. Methods: Herein, we propose an implantable micro-scale light-emitting diode device (micro-LED) guided PDT that enables the on-demand light activation of photosensitizers deep in the body to potentiate antitumor immunity with mild visible light. Results: The micro-LED is prepared by stacking one to four micro-scale LEDs (100 μm) on a needle-shape photonic device, which can be directly implanted into the core part of the tumor tissue. The photonic device with four LEDs efficiently elicits sufficient light output powers without thermal degradation and promotes reactive oxygen species (ROS) from a photosensitizer (verteporfin; VPF). After the intravenous injection of VPF in colon tumor-bearing mice, the tumor tissues are irradiated with optimal light intensity using an implanted micro-LED. While tumor tissues under intense visible light causes immunosuppression by severe inflammatory responses and regulatory T cell activation, mild visible light elicits potent ICD in tumor cells, which promotes dendritic cell (DC) maturation and T cell activation. The enhanced therapeutic efficacy and antitumor immunity by micro-LED guided PDT with mild visible light are assessed in colon tumor models. Finally, micro-LED guided PDT in combination with immune checkpoint blockade leads to 100% complete tumor regression and also establishes systemic immunological memory to prevent the recurrence of tumors. Conclusion: Collectively, this study demonstrates that micro-LED guided PDT with mild visible light is a promising strategy for cancer immunotherapy.