A Bone-Targeting Hydrogen Sulfide Delivery System for Treatment of Osteoporotic Fracture via Macrophage Reprogramming and Osteoblast-Osteoclast Coupling

Yi Qin; Zhen Zhang; Xiaobin Guo; Wenhao Li; Wenyu Xia; Gaoran Ge; Yanyue Li; Min Guan; Ang Gao; Lu Mao; Huaiyu Wang; Paul K. Chu; Dechun Geng

doi:10.1002/adfm.202418822

A Bone-Targeting Hydrogen Sulfide Delivery System for Treatment of Osteoporotic Fracture via Macrophage Reprogramming and Osteoblast-Osteoclast Coupling

Yi Qin
, Zhen Zhang
, Xiaobin Guo
, Wenhao Li
, Wenyu Xia
, Gaoran Ge
, Yanyue Li
, Min Guan
, Ang Gao^*
, Lu Mao^*
, Huaiyu Wang^*
, Paul K. Chu
, Dechun Geng^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

17 Citations (Scopus)

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 (H₂S) delivery system (ZIF-H₂S-SDSSD) is designed to simultaneously promote fracture healing and alleviate osteoporosis. With bone-targeting peptide SDSSD grafted on the surface, ZIF-H₂S-SDSSD nanoparticles release H₂S in bone tissues without affecting the serum H₂S level, thereby mitigating potential risks of systematic H₂S delivery. Upon cellular uptake, the acidic environment in lysosomes drives the release of H₂S from the encapsulated zinc sulfide in conjunction with the degradation of ZIF. The synergistic effects of released Zn²⁺ and H₂S 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. © 2024 Wiley-VCH GmbH.

Original language	English
Article number	2418822
Number of pages	17
Journal	Advanced Functional Materials
Volume	35
Issue number	17
Online published	23 Dec 2024
DOIs	https://doi.org/10.1002/adfm.202418822
Publication status	Published - 25 Apr 2025

Funding

This work was supported by the National Natural Science Foundation of China (82072425, 82072498, 82272567, 82350710800), the Natural Science Foundation of Jiangsu Province (BK2021650), the China Postdoctoral Science Foundation (No.:2017T100320), the Shenzhen Science and Technology Program (JCYJ20210324101800002), the Guangdong Basic and Applied Basic Research Foundation (2022A1515010528, 2024A1515012397), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Jiangsu Medical Research Project (ZD2022014), the Program of Suzhou Health Commission (GSWS2022002), the Tianshan Talent Training Program of Xinjiang Uygur Autonomous Region: Youth Support Talent Project (2023TSYCQNTJ0018), the National and Local Engineering Laboratory of New Functional Polymer Materials (SDGC2205), the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX22_3217), as well as City University of Hong Kong Donation Research Grants (Nos. DON-RMG 9229021 and 9229021).

Research Keywords

bone targeting
hydrogen sulfide
macrophage polarization
metabolic reprogramming
osteoporotic fracture

RGC Funding Information

RGC-funded

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10.1002/adfm.202418822

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Qin, Y., Zhang, Z., Guo, X., Li, W., Xia, W., Ge, G., Li, Y., Guan, M., Gao, A., Mao, L., Wang, H., Chu, P. K., & Geng, D. (2025). A Bone-Targeting Hydrogen Sulfide Delivery System for Treatment of Osteoporotic Fracture via Macrophage Reprogramming and Osteoblast-Osteoclast Coupling. Advanced Functional Materials, 35(17), Article 2418822. https://doi.org/10.1002/adfm.202418822

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title = "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 (H2S) delivery system (ZIF-H2S-SDSSD) is designed to simultaneously promote fracture healing and alleviate osteoporosis. With bone-targeting peptide SDSSD grafted on the surface, ZIF-H2S-SDSSD nanoparticles release H2S in bone tissues without affecting the serum H2S level, thereby mitigating potential risks of systematic H2S delivery. Upon cellular uptake, the acidic environment in lysosomes drives the release of H2S from the encapsulated zinc sulfide in conjunction with the degradation of ZIF. The synergistic effects of released Zn2+ and H2S 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. {\textcopyright} 2024 Wiley-VCH GmbH.",

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author = "Yi Qin and Zhen Zhang and Xiaobin Guo and Wenhao Li and Wenyu Xia and Gaoran Ge and Yanyue Li and Min Guan and Ang Gao and Lu Mao and Huaiyu Wang and Chu, \{Paul K.\} and Dechun Geng",

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A Bone-Targeting Hydrogen Sulfide Delivery System for Treatment of Osteoporotic Fracture via Macrophage Reprogramming and Osteoblast-Osteoclast Coupling. / Qin, Yi; Zhang, Zhen; Guo, Xiaobin et al.
In: Advanced Functional Materials, Vol. 35, No. 17, 2418822, 25.04.2025.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - A Bone-Targeting Hydrogen Sulfide Delivery System for Treatment of Osteoporotic Fracture via Macrophage Reprogramming and Osteoblast-Osteoclast Coupling

AU - Qin, Yi

AU - Zhang, Zhen

AU - Guo, Xiaobin

AU - Li, Wenhao

AU - Xia, Wenyu

AU - Ge, Gaoran

AU - Li, Yanyue

AU - Guan, Min

AU - Gao, Ang

AU - Mao, Lu

AU - Wang, Huaiyu

AU - Chu, Paul K.

AU - Geng, Dechun

PY - 2025/4/25

Y1 - 2025/4/25

N2 - 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 (H2S) delivery system (ZIF-H2S-SDSSD) is designed to simultaneously promote fracture healing and alleviate osteoporosis. With bone-targeting peptide SDSSD grafted on the surface, ZIF-H2S-SDSSD nanoparticles release H2S in bone tissues without affecting the serum H2S level, thereby mitigating potential risks of systematic H2S delivery. Upon cellular uptake, the acidic environment in lysosomes drives the release of H2S from the encapsulated zinc sulfide in conjunction with the degradation of ZIF. The synergistic effects of released Zn2+ and H2S 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. © 2024 Wiley-VCH GmbH.

AB - 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 (H2S) delivery system (ZIF-H2S-SDSSD) is designed to simultaneously promote fracture healing and alleviate osteoporosis. With bone-targeting peptide SDSSD grafted on the surface, ZIF-H2S-SDSSD nanoparticles release H2S in bone tissues without affecting the serum H2S level, thereby mitigating potential risks of systematic H2S delivery. Upon cellular uptake, the acidic environment in lysosomes drives the release of H2S from the encapsulated zinc sulfide in conjunction with the degradation of ZIF. The synergistic effects of released Zn2+ and H2S 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. © 2024 Wiley-VCH GmbH.

KW - bone targeting

KW - hydrogen sulfide

KW - macrophage polarization

KW - metabolic reprogramming

KW - osteoporotic fracture

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DO - 10.1002/adfm.202418822

M3 - RGC 21 - Publication in refereed journal

SN - 1616-301X

VL - 35

JO - Advanced Functional Materials

JF - Advanced Functional Materials

IS - 17

M1 - 2418822

ER -

A Bone-Targeting Hydrogen Sulfide Delivery System for Treatment of Osteoporotic Fracture via Macrophage Reprogramming and Osteoblast-Osteoclast Coupling

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Research Keywords

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A Bone-Targeting Hydrogen Sulfide Delivery System for Treatment of Osteoporotic Fracture via Macrophage Reprogramming and Osteoblast-Osteoclast Coupling

Abstract

Funding

Research Keywords

RGC Funding Information

Access Output

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Permanent Link

Other Files and Links

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DON_RMG: Fabrication, Characterization, and Properties of Functional Materials - RMGS

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