Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia immunity
Considerable advances have been achieved in the application of nanomaterials for immunotherapies, yet the precise immune effects induced by protein corona remain elusive. Here, we explore the formation mechanism and immune regulation process of protein corona in acute myeloid leukaemia (AML) mouse models using commercialized iron oxide nanoparticles (IONPs), with different surface modifications, including an FDA-approved variant. Using macrophages depleted or Complement Component 3 (C3) knockout mice, we demonstrate that carboxymethyl dextran-coated IONP (IONP-COOH) reduces leukaemia burden. Mechanistically, IONP-COOH indirectly binds to C3b after activating the complement alternative pathway, subsequently enhancing phagocytosis of macrophages and activating adaptive immunity mediated by complement corona. While aminated dextran-coated IONPs directly absorb C3b and activate the lectin pathway, leading to immune cell exhaustion. Our findings suggest that IONP-COOH may serve as an immune activator for AML treatment, offering a promising approach to developing therapeutic nanomaterials by leveraging surface chemistry to enhance immunotherapy.
Authors
- Jingyuan Wu (ORCID: https://orcid.org/0000-0002-0933-8556)
- Zizhun Wang
- Mingyuan Gao (ORCID: https://orcid.org/0000-0002-7360-3684)
- Yangyang Zhao (ORCID: https://orcid.org/0000-0002-0046-2091)
- Shuang Sun (ORCID: https://orcid.org/0000-0002-1274-0087)
- Wu Wen
- Haiyan Liu (ORCID: https://orcid.org/0000-0002-0672-5091)
- Wei Zhang (ORCID: https://orcid.org/0000-0002-6414-7015)
- Fangfang Chen (ORCID: https://orcid.org/0000-0002-3284-3331)
- Qiong Wu (ORCID: https://orcid.org/0009-0004-2230-2752)
- Ping Ren (ORCID: https://orcid.org/0000-0001-8694-8705)
- Bin Tian (ORCID: https://orcid.org/0000-0001-8903-8256)
- Jiarui Zhao (ORCID: https://orcid.org/0000-0003-1240-3811)
- Qihui Liu (ORCID: https://orcid.org/0000-0002-8985-1906)
- Xi Xi (ORCID: https://orcid.org/0000-0002-0175-5283)
- Y. Lv
- Yuan-Yuan Li (ORCID: https://orcid.org/0009-0006-8043-8900)
- Jiaqi Cui (ORCID: https://orcid.org/0000-0001-6006-4442)
Institutions
- Jilin University (CN)
- Soochow University (CN)
- First Hospital of Jilin University (CN)
- Union Hospital (CN)
- University of Colorado Anschutz Medical Campus (US)
- University of Montana (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-29
- DOI
- https://doi.org/10.1038/s41467-024-54810-0
- Citations
- 21
- Primary Topic
- Complement system in diseases
- Type
- article
- Field-Weighted Citation Impact
- 5.05
Funders
- Natural Science Foundation of Jilin Province
- National Natural Science Foundation of China
- Ministry of Science and Technology of the People's Republic of China
- China Postdoctoral Science Foundation
- People's Government of Jilin Province
- Jilin University
- National Key Research and Development Program of China