Synergistic Modulating of Mitochondrial Transfer and Immune Microenvironment to Attenuate Discogenic Pain
Discogenic pain, caused by intervertebral disc degeneration (IVDD), is a prevalent and challenging condition to treat effectively. Macrophage infiltration with neural ectopic in-growth resulting from structural disturbances within the intervertebral disc (IVD) is a major cause of discogenic pain. This work systematically reveals how nanoparticles can synergistically regulate the immune microenvironment and mitochondrial communication to attenuate discogenic pain. The antioxidant metal-polyphenol nanoparticle system can sequentially regulate macrophage phenotype and mitochondrial delivery efficiency. This strategy circumvents the necessity for mitochondrial isolation and preservation techniques that are typically required in conventional mitochondrial transplantation procedures. Furthermore, it facilitates the effective and sustained delivery of mitochondria to damaged cells. In vivo, this nanoparticle formulation effectively preserves the IVD height, maintains the structural integrity of the nucleus pulposus (NP), and restores pain thresholds. Thus, this nanoplatform offers an effective approach to traditional surgical treatments for discogenic pain, with significant potential for clinical application.
Authors
- Yunlong Zhou (ORCID: https://orcid.org/0000-0001-5654-1170)
- Kenny Yat-Hong Kwan (ORCID: https://orcid.org/0000-0002-4034-8525)
- Aimin Wu (ORCID: https://orcid.org/0000-0002-8582-4599)
- Yan Michael Li (ORCID: https://orcid.org/0000-0003-0989-260X)
- Qiuping Qian (ORCID: https://orcid.org/0000-0003-0260-736X)
- Pooyan Makvandi (ORCID: https://orcid.org/0000-0003-2456-0961)
- Yang‐Yang Hu (ORCID: https://orcid.org/0000-0001-7992-836X)
- Xinzhou Wang (ORCID: https://orcid.org/0000-0003-3972-3073)
- Zhenyu Guo (ORCID: https://orcid.org/0000-0003-0524-2693)
- Morgan Jones (ORCID: https://orcid.org/0000-0002-1532-7730)
- Linjie Chen (ORCID: https://orcid.org/0009-0007-7431-4490)
- Xiangyang Wang (ORCID: https://orcid.org/0000-0002-6504-2661)
- Jing Sun
- Xueqiang Wang (ORCID: https://orcid.org/0000-0001-7476-401X)
Institutions
- Chinese University of Hong Kong (HK)
- SUNY Upstate Medical University (US)
- Wenzhou Medical University (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Royal Orthopaedic Hospital (GB)
- Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University (CN)
- University of Chinese Academy of Sciences (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-03-27
- DOI
- https://doi.org/10.1002/advs.202500128
- Citations
- 6
- Primary Topic
- Pain Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 6.99
Funders
- National Natural Science Foundation of China