한빛사논문
- 조회311
이화여자대학교
Wan Su Yun1,2,#, Wonseok Yang2,#, Man Kyu Shim3,#, Sukyung Song1, Jiwoong Choi3, Jeongrae Kim1,2, Jinseong Kim1, Yujeong Moon3, SeongHoon Jo3, Dong-Kwon Lim2,4,5,*, Kwangmeyung Kim1,*
1College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea
2KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
3Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
4Department of Integrative Energy Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
5Brain Science Institute, Korea Institute of Science and Technology (KIST), 5, Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea
#These authors contributed equally to this work.
*Correspondence and requests for materials should be addressed to K. Kim or D.-K. Lim
Abstract
Photothermal therapy (PTT) at mild temperatures ranging from 44 to 45°C holds tremendous promise as a strategy for inducing potent immunogenic cell death (ICD) within tumor tissues, which can reverse the immunosuppressive tumor microenvironment (ITM) into an immune-responsive milieu. However, accurately and precisely controlling the tumor temperature remains a formidable challenge. Herein, we report the precision photothermal immunotherapy by using silica-coated gold nanorods (AuNR@SiO2), and investigating the optimal administration routes and treatment protocols, which enabled to achieve the sustained and controlled mild heating within the tumor tissues. First, the highest photothermal performance of AuNR@SiO2 with 20 nm silica shell thickness than 5 or 40 nm was confirmed in vitroand in vivo. Then, the optimal conditions for precision immunotherapy were further investigated to produce mild temperature (44 – 45°C) accurately in tumor tissues. The optimal conditions with AuNR@SiO2 result in a distinct cell death with high early/late apoptosis and low necrosis, leading to very efficient ICD compared to lower or higher temperatures. In colon tumor-bearing mice, intratumorally injected AuNR@SiO2 efficiently promote a mild temperature within the tumor tissues by local irradiation of NIR laser. This mild PTT significantly increases the population of mature dendritic cells (DCs) and cytotoxic T cells (CTLs) within tumor tissues, ultimately reversing the ITM into an immune-responsive milieu. Furthrmore, we found that the combination mild PTT with AuNR@SiO2 and anti-PD-L1 therapy could lead to the 100% complete regression of primary tumors and immunological memory to prevent tumor recurrence. Collectively, this study demonstrates AuNR@SiO2 with a robust methodology capable of continuously inducing mild temperature accurately within the ITM holds promise as an approach to achieve the precision photothermal immunotherapy.
논문정보
- Research article
- 2024년 03월 (BRIC 등록일 2024-04-23)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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