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Theranostics 2023; 13(3):1010-1027. doi:10.7150/thno.80514 This issue Cite

Research Paper

Ultrasmall PtAu2 nanoclusters activate endogenous anti-inflammatory and anti-oxidative systems to prevent inflammatory osteolysis

Xuzhuo Chen1*, Xiankun Cao3*, Dasheng Zheng2, Chang Li2, Yan Chen3, Keyu Kong3, Weifeng Xu1, Bin Shi4, Xinwei Chen1✉, Fengrong Dai2✉, Shanyong Zhang1✉

1. Department of Oral Surgery, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
2. State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, 350002, China.
3. Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
4. Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350002, Fujian, China.
*These authors contributed equally to this work.

✉ Corresponding authors: E-mail addresses: chenxinweiedu.cn (XW. Chen), dfrac.cn (FR. Dai), zhangshanyongcom (SY. Zhang).

Citation:
Chen X, Cao X, Zheng D, Li C, Chen Y, Kong K, Xu W, Shi B, Chen X, Dai F, Zhang S. Ultrasmall PtAu2 nanoclusters activate endogenous anti-inflammatory and anti-oxidative systems to prevent inflammatory osteolysis. Theranostics 2023; 13(3):1010-1027. doi:10.7150/thno.80514. https://www.thno.org/v13p1010.htm
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Abstract

Graphic abstract

Rationale: Inflammatory osteolysis, characterized by abundant immune cell infiltration and osteoclast (OC) formation, is a common complication induced by bacterial products and/or wear particles at the bone-prosthesis interface that severely reduces long-term stability after implantation. Molecular nanoclusters are ultrasmall particles with unique physicochemical and biological properties that have great potential as theranostic agents for treating inflammatory diseases.

Methods: In this study, heterometallic PtAu2 nanoclusters with sensitive nitric oxide-responsive phosphorescence turn-on characteristics and strong binding interactions with cysteine were designed, making them desirable candidates for the treatment of inflammatory osteolysis.

Results: PtAu2 clusters exhibited satisfactory biocompatibility and cellular uptake behavior, with potent anti-inflammatory and anti-OC activities in vitro. In addition, PtAu2 clusters alleviated lipopolysaccharide-induced calvarial osteolysis in vivo and activated nuclear factor erythroid 2-related factor 2 (Nrf2) expression by disrupting its association with Kelch-like ECH-associated protein 1 (Keap1), thereby upregulating the expression of endogenous anti-inflammatory and anti-oxidative products.

Conclusion: Through the rational design of novel heterometallic nanoclusters that activate the endogenous anti-inflammatory system, this study provides new insights into the development of multifunctional molecular therapeutic agents for inflammatory osteolysis and other inflammatory diseases.

Keywords: Metal cluster, Alloy cluster, Osteolysis, Osteoclast, Nrf2

Citation styles

APA
Chen, X., Cao, X., Zheng, D., Li, C., Chen, Y., Kong, K., Xu, W., Shi, B., Chen, X., Dai, F., Zhang, S. (2023). Ultrasmall PtAu2 nanoclusters activate endogenous anti-inflammatory and anti-oxidative systems to prevent inflammatory osteolysis. Theranostics, 13(3), 1010-1027. https://doi.org/10.7150/thno.80514.

ACS
Chen, X.; Cao, X.; Zheng, D.; Li, C.; Chen, Y.; Kong, K.; Xu, W.; Shi, B.; Chen, X.; Dai, F.; Zhang, S. Ultrasmall PtAu2 nanoclusters activate endogenous anti-inflammatory and anti-oxidative systems to prevent inflammatory osteolysis. Theranostics 2023, 13 (3), 1010-1027. DOI: 10.7150/thno.80514.

NLM
Chen X, Cao X, Zheng D, Li C, Chen Y, Kong K, Xu W, Shi B, Chen X, Dai F, Zhang S. Ultrasmall PtAu2 nanoclusters activate endogenous anti-inflammatory and anti-oxidative systems to prevent inflammatory osteolysis. Theranostics 2023; 13(3):1010-1027. doi:10.7150/thno.80514. https://www.thno.org/v13p1010.htm

CSE
Chen X, Cao X, Zheng D, Li C, Chen Y, Kong K, Xu W, Shi B, Chen X, Dai F, Zhang S. 2023. Ultrasmall PtAu2 nanoclusters activate endogenous anti-inflammatory and anti-oxidative systems to prevent inflammatory osteolysis. Theranostics. 13(3):1010-1027.

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