A Multi-Functional Nanoadjuvant Coupling Manganese with Toll-Like 9 Agonist Stimulates Potent Innate and Adaptive Anti-Tumor Immunity.

Autor: Liu Z; College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China.; NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial & Institute of Regulatory Science for Medical Device & National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, 610064, China., Li S; College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China., Xiao Y; College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China., Liu X; Orthopedic Research Institution, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610041, China., Zhang B; College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China., Zeng Q; College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China.; NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial & Institute of Regulatory Science for Medical Device & National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, 610064, China., Ao Q; College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China.; NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial & Institute of Regulatory Science for Medical Device & National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, 610064, China., Zhang X; College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China.; NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial & Institute of Regulatory Science for Medical Device & National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, 610064, China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Nov; Vol. 11 (41), pp. e2402678. Date of Electronic Publication: 2024 Sep 11.
DOI: 10.1002/advs.202402678
Abstrakt: The effectiveness of Toll-like 9 agonists (CpG) as an adjuvant for tumor immunotherapy is restricted due to their insufficient ability to activate anti-tumor immunity. To address that, the common nutrient metal ions are explored (Mn 2+ , Cu 2+ , Ca 2+ , Mg 2+ , Zn 2+ , Fe 3+ , and Al 3+ ), identifying Mn 2+ as a key enhancer of CpG to mediate immune activation by augmenting the STING-NF-κB pathway. Mn 2+ and CpG are then self-assembled with epigallocatechin gallate (EGCG) into a nanoadjuvant MPN/CpG. Local delivery of MPN/CpG effectively inhibits tumor growth in a B16 melanoma-bearing mouse model, reshaping the tumor microenvironment (TME) by repolarizing M2-type tumor-associated macrophages (TAMs) to an M1-type and boosting intra-tumoral infiltration of CD8 + /CD4 + T lymphocytes and DCs. Furthermore, compared to free CpG, MPN/CpG exhibits heightened accumulation in lymph nodes, enhancing CpG uptake and DC activation, consequently inducing significant antigen-specific cytotoxic CD8 + T cell immune response and humoral immunity. In a prophylactic tumor-bearing mouse model, MPN/CpG vaccination with OVA antigen significantly delays B16-OVA melanoma growth and extends mouse survival. These findings underscore the potential of MPN/CpG as a multifunctional adjuvant platform to drive powerful innate and adaptive immunity and regulate TME against tumors.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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