Jiwoong Choi1,2, Il Seong Lee1,2, Ju Seung Lee3, Sangmin Jeon1, Wan Su Yun1,2, Suah Yang1,2, Yujeong Moon1,4, Jinseong Kim1,2, Jeongrae Kim1,2, Seunghwan Choy5, Chanho Jeong6, Man Kyu Shim7, Tae-Il Kim8,9, Kwangmeyung Kim10,11,12. 1. Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, 02792, Seoul, Republic of Korea. 2. KU-KIST Graduate School of Converging Science and Technology, Korea University, 02841, Seoul, Republic of Korea. 3. School of Chemical Engineering, Sungkyunkwan University (SKKU), 16419, Suwon, Republic of Korea. 4. Department of Bioengineering, Korea University, 02841, Seoul, Republic of Korea. 5. Division of Digital Clinical Research, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, Republic of Korea. 6. Department of Biomedical Engineering, Sungkyunkwan University (SKKU), 16419, Suwon, Republic of Korea. 7. Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, 02792, Seoul, Republic of Korea. mks@kist.re.kr. 8. School of Chemical Engineering, Sungkyunkwan University (SKKU), 16419, Suwon, Republic of Korea. taeilkim@skku.edu. 9. Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), 16419, Suwon, Republic of Korea. taeilkim@skku.edu. 10. Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, 02792, Seoul, Republic of Korea. kimkm@ewha.ac.kr. 11. KU-KIST Graduate School of Converging Science and Technology, Korea University, 02841, Seoul, Republic of Korea. kimkm@ewha.ac.kr. 12. College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, 03760, Seoul, Republic of Korea. kimkm@ewha.ac.kr.
Abstract
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.
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.
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