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Self-Assembled STING-Activating Coordination Nanoparticles for Cancer Immunotherapy and Vaccine Applications.
Sun, Xiaoqi; Huang, Xuehui; Park, Kyung Soo; Zhou, Xingwu; Kennedy, Andrew A; Pretto, Carla D; Wu, Qi; Wan, Ziye; Xu, Yao; Gong, Wang; Sexton, Jonathan Z; Tai, Andrew W; Lei, Yu Leo; Moon, James J.
Afiliação
  • Sun X; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Huang X; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Park KS; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Zhou X; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Kennedy AA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Pretto CD; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Wu Q; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Wan Z; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Xu Y; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States.
  • Gong W; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States.
  • Sexton JZ; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Tai AW; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Lei YL; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Moon JJ; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.
ACS Nano ; 18(15): 10439-10453, 2024 Apr 16.
Article em En | MEDLINE | ID: mdl-38567994
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 Zn2+ and Mn2+ 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vacinas / Nanopartículas / Neoplasias Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vacinas / Nanopartículas / Neoplasias Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article