James J. Moon (University of Michigan) | 한빛사논문 > 한빛사

한빛사논문

조회155

University of Michigan

ACS Nano, Apr 16 2024, 18 (15) | https://doi.org/10.1021/acsnano.3c11374 Self-Assembled STING-Activating Coordination Nanoparticles for Cancer Immunotherapy and Vaccine Applications

Xiaoqi Sun ^1,2, Xuehui Huang^1,2, Kyung Soo Park ^2,3, Xingwu Zhou ^1,2, Andrew A Kennedy ⁴, Carla D Pretto 4, Qi Wu ^1,2, Ziye Wan ^1,2, Yao Xu ^1,2, Wang Gong ^5,6, Jonathan Z Sexton ^4,7, Andrew W Tai ^4,8, Yu Leo Lei^5,9,10,11, James J. Moon ^1,2,3,10,12

¹Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.

²Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.

³Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.

⁴Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States.

⁵Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States.

⁶Department of Cancer Biology at the University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77030, United States.

⁷Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.

⁸Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States.

⁹Department of Otolaryngology─Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109, United States.

¹⁰Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, United States.

¹¹Department of Head and Neck Surgery, Department of Cancer Biology, Department of Translational Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, United States.

¹²Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.

X.S., X.H., K.S.P., and X. Z. contributed equally to this work.

Corresponding Author: James J. Moon

Abstract

The cGAS-STING pathway plays a crucial role in innate immune activation against cancer and infections, and STING agonists based on cyclic dinucleotides (CDN) have garnered attention for their potential use in cancer immunotherapy and vaccines. However, the limited drug-like properties of CDN necessitate an efficient delivery system to the immune system. To address these challenges, we developed an immunostimulatory delivery system for STING agonists. Here, we have examined aqueous coordination interactions between CDN and metal ions and report that CDN mixed with Zn ²⁺ and Mn ²⁺ formed distinctive crystal structures. Further pharmaceutical engineering led to the development of a functional coordination nanoparticle, termed the Zinc-Mn-CDN Particle (ZMCP), produced by a simple aqueous one-pot synthesis. Local or systemic administration of ZMCP exerted robust antitumor efficacy in mice. Importantly, recombinant protein antigens from SARS-CoV-2 can be simply loaded during the aqueous one-pot synthesis. The resulting ZMCP antigens elicited strong cellular and humoral immune responses that neutralized SARS-CoV-2, highlighting ZMCP as a self-adjuvant vaccine platform against COVID-19 and other infectious pathogens. Overall, this work establishes a paradigm for developing translational coordination nanomedicine based on drug-metal ion coordination and broadens the applicability of coordination medicine for the delivery of proteins and other biologics.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-05-22)
연구진국외 연구진
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