Homotransplantation of Engineered Macrophages with Surface-Modified Nanomedicines for Mitigating Myocardial Ischemia–Reperfusion Injury
Immune disorders are intimately involved in the pathological progression of myocardial ischemia-reperfusion injury (MIRI) and exacerbate cardiac cell damage and mitochondria-related metabolic abnormalities. However, low-immunogenic therapeutic strategies targeting the compromised immune-metabolic microenvironment remain a major challenge. Here, we developed a syngenic reparative macrophage system for the selective delivery of nanoscale drugs by modifying liposomes loaded with nano-Pt/Se and c176 onto the surface of M2 macrophages (PS-c@M). In MIRI mice, transplanted PS-c@M was actively recruited to the myocardial ischemic region, maintained long-lasting residence, and responsively released surface-loaded nanomedicines, which in turn synergistically promoted cardiac cell survival and activated extracellular repair and angiogenesis, thus exerting long-term cardioprotective effects. Specifically, PS-c@M significantly inhibited STING-related signaling pathways, thereby remodeling the immune-inflammatory homeostasis, as evidenced by the increased proportions of M2 macrophages, reparative cardiac resident macrophages, and regulatory T cells and the decreased recruitment and infiltration of M1 macrophages and neutrophils. Moreover, PS-c@M facilitated mitochondrial oxidative phosphorylation and suppressed mitochondria-associated ferroptosis and oxidative damage. This study highlights a low-immunogenic targeted therapeutic strategy based on syngenic reparative macrophages as efficient nanomedicine carriers, with potential for development and application in a wide range of immune and inflammation-related diseases.
Authors
- Lian‐Ming Wu (ORCID: https://orcid.org/0000-0001-7381-5436)
- Lingling Xu (ORCID: https://orcid.org/0000-0002-0243-9004)
- Yuzhuo Li
- Rifeng Gao (ORCID: https://orcid.org/0000-0002-5453-8899)
- Yang Lyu (ORCID: https://orcid.org/0000-0002-4353-0082)
- Lixian Jiang (ORCID: https://orcid.org/0000-0002-8377-4399)
- Zhiqiang Ji (ORCID: https://orcid.org/0000-0003-4542-0220)
- Shiteng Suo (ORCID: https://orcid.org/0000-0003-2528-2836)
- Bo Li (ORCID: https://orcid.org/0000-0001-9476-3073)
- Qiang Zhang (ORCID: https://orcid.org/0009-0008-8671-4659)
- Wen Wang
- Peng Guo (ORCID: https://orcid.org/0000-0001-8265-4072)
- Wenli Li (ORCID: https://orcid.org/0000-0003-1598-3217)
- Jinli Zhang (ORCID: https://orcid.org/0000-0001-5805-3824)
- Yan Zhou (ORCID: https://orcid.org/0000-0001-9402-1109)
- Zhi Xiong (ORCID: https://orcid.org/0000-0003-4343-9104)
- Huilin Zhao (ORCID: https://orcid.org/0000-0003-3023-5292)
- Jiahui Cheng (ORCID: https://orcid.org/0000-0001-8801-3399)
- Xu Han (ORCID: https://orcid.org/0000-0002-6936-8984)
- Weina Ding
- Xiaoyu Huang (ORCID: https://orcid.org/0000-0002-7479-6078)
- Xinxin Zhao
- Kun Yang (ORCID: https://orcid.org/0000-0003-3146-3828)
- Lin Guo (ORCID: https://orcid.org/0000-0002-1337-4875)
Institutions
- Shanghai Jiao Tong University (CN)
- Fudan University (CN)
- Renji Hospital (CN)
- Zhengzhou University (CN)
- Huadong Hospital (CN)
- Shanghai Sixth People's Hospital (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
Publication Details
- Journal
- ACS Nano
- Published
- 2025-06-27
- DOI
- https://doi.org/10.1021/acsnano.5c05068
- Citations
- 12
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 9.67
Funders
- Shanghai Municipal Health Commission
- National Natural Science Foundation of China
- Science and Technology Commission of Shanghai Municipality
- Shanghai Municipal Human Resources and Social Security Bureau
- Renji Hospital
- Shanghai Shuguang Program
- National Program for Support of Top-notch Young Professionals