A Bone‐Targeting Hydrogen Sulfide Delivery System for Treatment of Osteoporotic Fracture via Macrophage Reprogramming and Osteoblast‐Osteoclast Coupling
Abstract The demand for systemic treatment of osteoporotic fractures to reduce recurrence is increasing, but current anti‐osteoporosis medications exhibit unsatisfactory efficacy due to adverse events and limited effects on fracture healing. Herein, a bone‐targeting zeolitic imidazolate framework‐8 (ZIF)‐based hydrogen sulfide (H 2 S) delivery system (ZIF‐H 2 S‐SDSSD) is designed to simultaneously promote fracture healing and alleviate osteoporosis. With bone‐targeting peptide SDSSD grafted on the surface, ZIF‐H 2 S‐SDSSD nanoparticles release H 2 S in bone tissues without affecting the serum H 2 S level, thereby mitigating potential risks of systematic H 2 S delivery. Upon cellular uptake, the acidic environment in lysosomes drives the release of H 2 S from the encapsulated zinc sulfide in conjunction with the degradation of ZIF. The synergistic effects of released Zn 2+ and H 2 S promote macrophage metabolic reprogramming by suppressing succinate accumulation and mitochondrial reactive oxygen species (mtROS) production, and further regulate osteoblast‐osteoclast coupling. Overall, this strategy holds great promise in the clinical treatment of osteoporotic fractures and broadens the application of nanomedicine therapy for orthopedic diseases.
Authors
- Gaoran Ge (ORCID: https://orcid.org/0000-0002-5535-7483)
- Xiaobin Guo (ORCID: https://orcid.org/0000-0003-1708-838X)
- Wenyu Xia (ORCID: https://orcid.org/0009-0001-5946-9212)
- Min Guan (ORCID: https://orcid.org/0000-0003-3851-8553)
- Yushan Li (ORCID: https://orcid.org/0000-0003-4224-8031)
- Lu Mao (ORCID: https://orcid.org/0000-0003-4868-6091)
- Dechun Geng (ORCID: https://orcid.org/0000-0003-4375-2803)
- Yi Qin (ORCID: https://orcid.org/0000-0001-8245-8207)
- Paul Kim-Ho Chu (ORCID: https://orcid.org/0000-0002-5581-4883)
- Wenhao Li (ORCID: https://orcid.org/0000-0002-6411-4539)
- Huaiyu Wang (ORCID: https://orcid.org/0000-0002-7189-9944)
- Ang Gao (ORCID: https://orcid.org/0000-0002-9013-0962)
- Zhen Zhang (ORCID: https://orcid.org/0009-0006-8239-6652)
Institutions
- Xinjiang Medical University (CN)
- City University of Hong Kong (HK)
- Chinese Academy of Sciences (CN)
- First Affiliated Hospital of Xinjiang Medical University (CN)
- Soochow University (CN)
- Zhongda Hospital Southeast University (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- First Affiliated Hospital of Soochow University (CN)
Publication Details
- Journal
- Advanced Functional Materials
- Published
- 2024-12-23
- DOI
- https://doi.org/10.1002/adfm.202418822
- Citations
- 17
- Primary Topic
- Sulfur Compounds in Biology
- Type
- article
- Field-Weighted Citation Impact
- 5.01
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Natural Science Foundation of Jiangsu Province
- Shenzhen Science and Technology Innovation Program
- Basic and Applied Basic Research Foundation of Guangdong Province