Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia immunity
Abstract 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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-11-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54810-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846147613932388352 |
|---|---|
| author | Yuanyuan Li Wen Wu Qihui Liu Qiong Wu Ping Ren Xi Xi Haiyan Liu Jiarui Zhao Wei Zhang Zizhun Wang Yuanyuan lv Bin Tian Shuang Sun Jiaqi Cui Yangyang Zhao Jingyuan Wu Mingyuan Gao Fangfang Chen |
| author_facet | Yuanyuan Li Wen Wu Qihui Liu Qiong Wu Ping Ren Xi Xi Haiyan Liu Jiarui Zhao Wei Zhang Zizhun Wang Yuanyuan lv Bin Tian Shuang Sun Jiaqi Cui Yangyang Zhao Jingyuan Wu Mingyuan Gao Fangfang Chen |
| author_sort | Yuanyuan Li |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-ab402e55649542cf88501cce1b46e92d |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ab402e55649542cf88501cce1b46e92d2024-12-01T12:35:32ZengNature PortfolioNature Communications2041-17232024-11-0115111610.1038/s41467-024-54810-0Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia immunityYuanyuan Li0Wen Wu1Qihui Liu2Qiong Wu3Ping Ren4Xi Xi5Haiyan Liu6Jiarui Zhao7Wei Zhang8Zizhun Wang9Yuanyuan lv10Bin Tian11Shuang Sun12Jiaqi Cui13Yangyang Zhao14Jingyuan Wu15Mingyuan Gao16Fangfang Chen17Key Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityThe Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical CampusKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityElectron Microscopy Center, Jilin UniversityElectron Microscopy Center, Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityState Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, School for Radiological and Interdisciplinary Sciences, Soochow UniversityKey Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin UniversityAbstract 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.https://doi.org/10.1038/s41467-024-54810-0 |
| spellingShingle | Yuanyuan Li Wen Wu Qihui Liu Qiong Wu Ping Ren Xi Xi Haiyan Liu Jiarui Zhao Wei Zhang Zizhun Wang Yuanyuan lv Bin Tian Shuang Sun Jiaqi Cui Yangyang Zhao Jingyuan Wu Mingyuan Gao Fangfang Chen Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia immunity Nature Communications |
| title | Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia immunity |
| title_full | Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia immunity |
| title_fullStr | Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia immunity |
| title_full_unstemmed | Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia immunity |
| title_short | Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia immunity |
| title_sort | specific surface modified iron oxide nanoparticles trigger complement dependent innate and adaptive antileukaemia immunity |
| url | https://doi.org/10.1038/s41467-024-54810-0 |
| work_keys_str_mv | AT yuanyuanli specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT wenwu specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT qihuiliu specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT qiongwu specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT pingren specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT xixi specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT haiyanliu specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT jiaruizhao specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT weizhang specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT zizhunwang specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT yuanyuanlv specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT bintian specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT shuangsun specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT jiaqicui specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT yangyangzhao specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT jingyuanwu specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT mingyuangao specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity AT fangfangchen specificsurfacemodifiedironoxidenanoparticlestriggercomplementdependentinnateandadaptiveantileukaemiaimmunity |