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

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机构： [1]College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China. [2]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. [3]Orthopedic Research Institution, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610041, China.

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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 (Mn2+, Cu2+, Ca2+, Mg2+, Zn2+, Fe3+, and Al3+), identifying Mn2+ as a key enhancer of CpG to mediate immune activation by augmenting the STING-NF-κB pathway. Mn2+ 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.

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出版当年[2023]版：

大类 | 1 区

材料科学

小类 | 1 区化学：综合 1 区材料科学：综合 2 区纳米科技

最新[2023]版：

大类 | 1 区

材料科学

小类 | 1 区化学：综合 1 区材料科学：综合 2 区纳米科技

第一作者：

第一作者机构： [1]College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China. [2]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.

通讯作者：

通讯机构： [1]College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China. [2]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.

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