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Qihang DingQihang Ding

고려대학교

J. Am. Chem. Soc., Mar 21 2024, | https://doi.org/10.1021/jacs.3c13224 Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle

Le Tu ¹⁺, Chonglu Li ^1,2+, Qihang Ding ³⁺, Amit Sharma ⁴⁺, Meiqin Li ¹⁺, Junrong Li ¹, Jong Seung Kim^3*, Yao Sun^1*

¹National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China.

²State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, China.

³Department of Chemistry, Korea University, Seoul 02841, Korea.

⁴Amity School of Chemical Sciences, Amity University Punjab, Sector 82A, Mohali, Punjab 140306, India.

⁺L.T., C.L., Q.D., A.S., and M.L. contributed equally to this work.

Corresponding Authors : Jong Seung Kim, Yao Sun

Abstract

Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with minimal side effects in deep-seated tumors remains challenging. Herein, we introduce a novel self-assembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105 (λ _em = 1105 nm), as a first example of a Ru(II) supramolecular ICD inducer. Ru1105 synergistically potentiates immunomodulatory responses and reduces adverse effects in deep-seated tumors through multiple regulated approaches, including NIR-light excitation, increased reactive oxygen species (ROS) generation, selective targeting of tumor cells, precision organelle localization, and improved tumor penetration/retention capabilities. Specifically, Ru1105 demonstrates excellent depth-activated ROS production (∼1 cm), strong resistance to diffusion, and anti-ROS quenching. Moreover, Ru1105 exhibits promising results in cellular uptake and ROS generation in cancer cells and multicellular tumor spheroids. Importantly, Ru1105 induces more efficient ICD in an ultralow dose (10 μM) compared to the conventional anticancer agent, oxaliplatin (300 μM). In vivo experiments further confirm Ru1105's potency as an ICD inducer, eliciting CD8 ⁺ T cell responses and depleting Foxp3 ⁺ T cells with minimal adverse effects. Our research lays the foundation for the design of secure and exceptionally potent metal-based ICD agents in immunotherapy.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-04-02)
연구진국내(교신)+국외 연구진
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