journal article·2025-03-05

Augmenting Antitumor Immune Effects through the Coactivation of cGAS-STING and NF-κB Crosstalk in Dendritic Cells and Macrophages by Engineered Manganese Ferrite Nanohybrids

Heying Chen, Dongqing Wang, Jiahe Liu, Jun Chen, Yi Hu, Yilu Ni

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Abstract

The specific activation of dendritic cells (DCs) and tumor-associated macrophages (TAMs) can activate innate and adaptive immune responses to reverse the tumor immunosuppressive microenvironment. In this study, manganese ferrite nanohybrid MnFe 5 O 8 @(M1M-DOX) is synthesized to activate cGAS-STING and NF-κB crosstalk in DCs and TAMs. MnFe 5 O 8, as the source of Fe 2+ /Fe 3+ and Mn 2+, is encapsulated with a microdose of doxorubicin (DOX) using an M1 macrophage cytomembrane. Fe 2+ /Fe 3+ and DOX can cooperatively induce tumorous ferroptosis, triggering immunogenic cell death (ICD) that exposes tumor antigens. The release of Fe 2+ /Fe 3+ and Mn 2+ has intrinsic dual-immunomodulatory effects on the activation of DCs and the reprogramming of TAMs from the M2 to M1 phenotype. Briefly, Fe 2+ /Fe 3+ activates the NF-κB signaling pathway to trigger the activation of STING signaling. Meanwhile, Mn 2+ further enhances the activation of STING and stimulates NF-κB in a cascade-activating manner. Thus, the mutually reinforcing dual activation of cGAS-STING and NF-κB crosstalk prompts the strong maturation of DCs and TAMs, synergistically promoting the infiltration of T cells to inhibit primary tumor growth and localized recurrence. This work proposes a strategy for delivering immunomodulatory metal ions in nanoalloy and harnessing the activation of multisignaling pathways in antigen-presenting cells (APCs) to provide perspectives for tumor immunotherapy.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Immune cells in cancer · Phagocytosis and Immune Regulation · interferon and immune responses

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

The Key Laboratory of Chinese Ministry of Education in Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, #1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China

Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital

Sichuan University

Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital

University of Electronic Science and Technology of China

Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong 999077, China

Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety

Institute of High Energy Physics and University of Chinese Academy of Sciences, Chinese Academy of Sciences

State Key Laboratory of Complex Severe and Rare Diseases, Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Peking Union Medical College Hospital

Chinese Academy of Medical Sciences and Peking Union Medical College

Funding

Natural Science Foundation of Chongqing Municipality · Ministry of Human Resources and Social Security · National Natural Science Foundation of China · National High Level Hospital Clinical Research · Sichuan Provincial People?s Hospital Research Fund

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