Adaptive Nanoparticle-Mediated Modulation of Mitochondrial Homeostasis and Inflammation to Enhance Infected Bone Defect Healing
Abstract
Infected bone defects (IBDs) exhibit impaired healing due to excessive inflammation triggered by pathogen-associated molecular patterns (PAMPs) from bacteria. As a vital factor in orchestrating immune responses, mitochondrial homeostasis maintenance is central to inflammation blockade. This research developed a chameleon-like nanoplatform by covering hydroxyapatite nanoparticles with a cerium ion coordinated tannic acid supramolecular network (HA@Ce-TA), which adaptively functions to regulate mitochondrial homeostasis based on intra- and extracellular environments. Extracellularly, acidic conditions activate HA@Ce-TA’s peroxidase/oxidase-mimicking activity to produce reactive oxygen species (ROS), and external near-infrared (NIR) irradiation excites nanoscale Ce-TA to produce hyperthermia, which is found and explained by chemical computation. ROS production with photothermal therapy can eliminate bacteria effectively and reduce mitochondrial stress. Intracellularly, HA@Ce-TA remodels mitochondrial dynamics by upregulating mitochondrial fusion genes and eliminates excessive ROS by mimicking superoxidase/catalase. Consequently, this comprehensive modulation of mitochondrial homeostasis inhibits inflammasome overactivation. In vitro and in vivo studies showed HA@Ce-TA can modulate the mitochondria-centered inflammatory cascade to enhance IBD treatment, highlighting the potential of engineering nanotherapeutics to recalibrate mitochondrial homeostasis as an infected disease-modifying intervention.
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In dental applications, the TA component alleviates inflammation via ROS scavenging and inhibits oral pathogens, reducing infection risk while promoting bone regeneration.
“In dental applications, the TA component simultaneously alleviates inflammation via ROS scavenging and inhibits oral pathogens60, reducing infection risk while promoting bone regeneration.”
From Intelligence-responsive wettability switch coating on magnesium implants for treating osteoporotic fracture (2026) · cites this paper as [60]
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Self-citation
- Authors
- Chen, X., He, Q., Zhai, Q., Tang, H., Li, D., Zhu, X., Zheng, X., Jian, G., Cannon, R. D., Mei, L., Wang, S., Ji, P., Song, J., & Chen, T.
- Affiliations
- Stomatological Hospital of Chongqing Medical University (CN)
- University of Otago (NZ)
- Department of Oral Sciences, Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin 9054, New Zealand
- Corresponding author
- Ji, Ping
- Song, Jinlin
- Chen, Tao
- ORCID
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2023-11-06
- Volume
- 17
- Issue
- 22
- Pages
- 22960-22978
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W4388410723
- Cited by
- 78
- References
- 66
- Citations by year
- 2026: 19 · 2025: 44 · 2024: 15
- FWCI
- 5.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chongqing Medical University (W0077)
- Science Fund for Distinguished Young Scholars of Chongqing Municipality (CSTB2022NSCQ-JQX0012)
- National Natural Science Foundation of China (32071362, 82201059, 82220108019, 31871464)
- Chongqing Municipality (CYB22215)
- Chongqing Young and Middle-Aged Medical Excellence Team
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Advanced Nanomaterials in Catalysis
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- infected bone defects, mitochondrial homeostasis, inflammation, hydroxyapatite nanoparticles, supramolecular networks, reactive oxygen species, photothermal therapy, hyperthermia, mitochondrial dynamics, mitochondrial fusion, inflammasome, bone regeneration, nanotherapeutics
- MeSH terms
- Antioxidants, Homeostasis, Humans, Inflammation, Mitochondria, Reactive Oxygen Species, Nanoparticles
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