Skip to main content

Advertisement

SpringerLink
Log in

Ångstrom-scale silver particles ameliorate collagen-induced and K/BxN-transfer arthritis in mice via the suppression of inflammation and osteoclastogenesis

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective

Nanoparticles (NPs) hold a great promise in combating rheumatoid arthritis, but are often compromised by their toxicities because the currently used NPs are usually synthesized by chemical methods. Our group has previously fabricated Ångstrom-scale silver particles (AgÅPs) and demonstrated the anti-tumor and anti-sepsis efficacy of fructose-coated AgÅPs (F-AgÅPs). This study aimed to uncover the efficacy and mechanisms of F-AgÅPs for arthritis therapy.

Methods

We evaluated the efficacy of F-AgÅPs in collagen-induced arthritis (CIA) mice. We also compared the capacities of F-AgÅPs, the commercial AgNPs, and the clinical drug methotrexate (MTX) in protecting against K/BxN serum-transfer arthritis (STA) mice. Moreover, we evaluated the effects of F-AgÅPs and AgNPs on inflammation, osteoclast formation, synoviocytes migration, and matrix metalloproteinases (MMPs) production in vitro and in vivo. Meanwhile, the toxicities of F-AgÅPs and AgNPs in vitro and in vivo were also tested.

Results

F-AgÅPs significantly prevented bone erosion, synovitis, and cartilage damage, attenuated rheumatic pain, and improved the impaired motor function in mouse models of CIA or STA, the anti-rheumatic effects of which were comparable or stronger than AgNPs and MTX. Further studies revealed that F-AgÅPs exhibited similar or greater inhibitory abilities than AgNPs to suppress inflammation, osteoclast formation, synoviocytes migration, and MMPs production. No obvious toxicities were observed in vitro and in vivo after F-AgÅPs treatment.

Conclusions

F-AgÅPs can effectively alleviate arthritis without notable toxicities and their anti-arthritic effects are associated with the inhibition of inflammation, osteoclastogenesis, synoviocytes migration, and MMPs production. Our study suggests the prospect of F-AgÅPs as an efficient and low-toxicity agent for arthritis therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

RA:

Rheumatoid arthritis

AgÅPs:

Ångstrom-scale silver particles

F-AgÅPs:

Fructose-coated AgÅPs

NSAIDs:

Non-steroidal anti-inflammatory drugs

SAARDs:

Slow-acting anti-rheumatic drugs

NPs:

Nanoparticles

AgNPs:

Nanometer-scale silver particles

CIA:

Collagen-induced arthritis

MTX:

Methotrexate

STA:

K/BxN serum-transfer arthritis

MMP:

Matrix metalloproteinase

DAB:

Diaminobenzidine tetrahydrochloride

BMMs:

Primary murine bone marrow macrophages

FBS:

Fetal bovine serum

M‐CSF:

Recombinant murine macrophage colony‐stimulating factor

PS:

Penicillin–streptomycin

SD:

Standard deviation

ANOVA:

Analysis of variance

References

  1. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388:2023–38.

    Article  CAS  PubMed  Google Scholar 

  2. Muller-Ladner U, Pap T, Gay RE, Neidhart M, Gay S. Mechanisms of disease: the molecular and cellular basis of joint destruction in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2005;1:102–10.

    Article  PubMed  Google Scholar 

  3. Rheumatoid arthritis. Nat Rev Dis Primers. 2018; 4: 18002.

  4. Corrado A, Rotondo C, Mele A, Cici D, Maruotti N, Sanpaolo E, et al. Influence of glucocorticoid treatment on trabecular bone score and bone remodeling regulators in early rheumatoid arthritis. Arthritis Res Ther. 2021;23:180.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Smolen JS, Steiner G. Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov. 2003;2:473–88.

    Article  CAS  PubMed  Google Scholar 

  6. Zhang S, Wu L, Cao J, Wang K, Ge Y, Ma W, et al. Effect of magnetic nanoparticles size on rheumatoid arthritis targeting and photothermal therapy. Colloids Surf B Biointerfaces. 2018;170:224–32.

    Article  CAS  PubMed  Google Scholar 

  7. Jeong M, Park JH. Nanomedicine for the treatment of rheumatoid arthritis. Mol Pharm. 2021;18:539–49.

    Article  CAS  PubMed  Google Scholar 

  8. Avalos A, Haza AI, Mateo D, Morales P. Cytotoxicity and ROS production of manufactured silver nanoparticles of different sizes in hepatoma and leukemia cells. J Appl Toxicol. 2014;34:413–23.

    Article  CAS  PubMed  Google Scholar 

  9. Miethling-Graff R, Rumpker R, Richter M, Verano-Braga T, Kjeldsen F, Brewer J, et al. Exposure to silver nanoparticles induces size- and dose-dependent oxidative stress and cytotoxicity in human colon carcinoma cells. Toxicol In Vitro. 2014;28:1280–9.

    Article  CAS  PubMed  Google Scholar 

  10. Wang ZX, Chen CY, Wang Y, Li FXZ, Huang J, Luo ZW, et al. Ångstrom-scale silver particles as a promising agent for low-toxicity broad-spectrum potent anticancer therapy. Adv Funct Mater. 2019;29:1808556.

    Article  Google Scholar 

  11. Kuang X, Wang Z, Luo Z, He Z, Liang L, Gao Q, et al. Ag nanoparticles enhance immune checkpoint blockade efficacy by promoting of immune surveillance in melanoma. J Colloid Interface Sci. 2022;616:189–200.

    Article  CAS  PubMed  Google Scholar 

  12. Deng YQ, Wang ZX, Liu X, Wang YY, Chen Q, Li ZL, et al. Angstrom-scale silver particles potently combat SARS-CoV-2 infection by suppressing the ACE2 expression and inflammatory responses. J Mater Chem B. 2022;10:5454–64.

    Article  CAS  PubMed  Google Scholar 

  13. Li YY, Xia K, Liu YW, Tan YJ, Li HM, Wang YY, et al. Fructose-coated angstrom silver particles suppress gastric cancer growth by activating gasdermin D-mediated pyroptosis. Adv Ther. 2023;6:2200100.

    Article  CAS  Google Scholar 

  14. Hu XK, Rao SS, Tan YJ, Yin H, Luo MJ, Wang ZX, et al. Fructose-coated angstrom silver inhibits osteosarcoma growth and metastasis via promoting ROS-dependent apoptosis through the alteration of glucose metabolism by inhibiting PDK. Theranostics. 2020;10:7710–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yin H, Zhou M, Chen X, Wan TF, Jin L, Rao SS, et al. Fructose-coated angstrom silver prevents sepsis by killing bacteria and attenuating bacterial toxin-induced injuries. Theranostics. 2021;11:8152–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chen CY, Yin H, Chen X, Chen TH, Liu HM, Rao SS, et al. Ångstrom-scale silver particle-embedded carbomer gel promotes wound healing by inhibiting bacterial colonization and inflammation. Sci Adv. 2020;6:eaba0942.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Brand DD, Latham KA, Rosloniec EF. Collagen-induced arthritis. Nat Protoc. 2007;2:1269–75.

    Article  CAS  PubMed  Google Scholar 

  18. Monach PA, Mathis D, Benoist C. The K/BxN arthritis model. Curr Protoc Immunol. 2008. https://doi.org/10.1002/0471142735.im1522s81.

    Article  PubMed  Google Scholar 

  19. Liu R, Chen Y, Fu W, Wang S, Cui Y, Zhao X, et al. Fexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against inflammatory arthritis. Ann Rheum Dis. 2019;78:1524–35.

    Article  CAS  PubMed  Google Scholar 

  20. Jin Y, Liu Q, Chen P, Zhao S, Jiang W, Wang F, et al. A novel prostaglandin E receptor 4 (EP4) small molecule antagonist induces articular cartilage regeneration. Cell Discov. 2022;8:24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hu X, Liu Y, Wu J, Liu Y, Liu W, Chen J, et al. Inhibition of P2X7R in the amygdala ameliorates symptoms of neuropathic pain after spared nerve injury in rats. Brain Behav Immun. 2020;88:507–14.

    Article  CAS  PubMed  Google Scholar 

  22. Wei K, Korsunsky I, Marshall JL, Gao A, Watts GFM, Major T, et al. Notch signalling drives synovial fibroblast identity and arthritis pathology. Nature. 2020;582:259–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Levescot A, Chang MH, Schnell J, Nelson-Maney N, Yan J, Martinez-Bonet M, et al. IL-1beta-driven osteoclastogenic tregs accelerate bone erosion in arthritis. J Clin Invest. 2021. https://doi.org/10.1172/JCI141008.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Fatima F, Fei Y, Ali A, Mohammad M, Erlandsson MC, Bokarewa MI, et al. Radiological features of experimental staphylococcal septic arthritis by micro computed tomography scan. PLoS ONE. 2017;12: e0171222.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Liu ZZ, Hong CG, Hu WB, Chen ML, Duan R, Li HM, et al. Autophagy receptor OPTN (optineurin) regulates mesenchymal stem cell fate and bone-fat balance during aging by clearing FABP3. Autophagy. 2021;17:2766–82.

    Article  CAS  PubMed  Google Scholar 

  26. Auréal M, Machuca-Gayet I, Coury F. Rheumatoid arthritis in the view of osteoimmunology. Biomolecules. 2020;11:48.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Lefèvre S, Knedla A, Tennie C, Kampmann A, Wunrau C, Dinser R, et al. Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat Med. 2009;15:1414–20.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci. 2006;11:529–43.

    Article  CAS  PubMed  Google Scholar 

  29. Wang D, Zhang J, Lau J, Wang S, Taneja V, Matteson EL, et al. Mechanisms of lung disease development in rheumatoid arthritis. Nat Rev Rheumatol. 2019;15:581–96.

    Article  PubMed  Google Scholar 

  30. Kalashnikova I, Chung SJ, Nafiujjaman M, Hill ML, Siziba ME, Contag CH, et al. Ceria-based nanotheranostic agent for rheumatoid arthritis. Theranostics. 2020;10:11863–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wu H, He Y, Wu H, Zhou M, Xu Z, Xiong R, et al. Near-infrared fluorescence imaging-guided focused ultrasound-mediated therapy against rheumatoid arthritis by MTX-ICG-loaded iRGD-modified echogenic liposomes. Theranostics. 2020;10:10092–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Li Y, Liang Q, Zhou L, Cao Y, Yang J, Li J, et al. An ROS-responsive artesunate prodrug nanosystem co-delivers dexamethasone for rheumatoid arthritis treatment through the HIF-1alpha/NF-kappaB cascade regulation of ROS scavenging and macrophage repolarization. Acta Biomater. 2022;152:406–24.

    Article  CAS  PubMed  Google Scholar 

  33. Han Y, Wang J, Li S, Li Y, Zhang Y, Zhang R, et al. Isopsoralen ameliorates rheumatoid arthritis by targeting MIF. Arthritis Res Ther. 2021;23:243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Park JS, Yang SC, Jeong HY, Lee SY, Ryu JG, Choi JW, et al. EC-18 prevents autoimmune arthritis by suppressing inflammatory cytokines and osteoclastogenesis. Arthritis Res Ther. 2022;24:254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhai Z, Yang F, Xu W, Han J, Luo G, Li Y, et al. Attenuation of rheumatoid arthritis through the inhibition of tumor necrosis factor-induced caspase 3/gasdermin E-mediated pyroptosis. Arthritis Rheumatol. 2022;74:427–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fukui S, Gutch S, Fukui S, Cherpokova D, Aymonnier K, Sheehy CE, et al. The prominent role of hematopoietic peptidyl arginine deiminase 4 in arthritis: collagen- and granulocyte colony-stimulating factor-induced arthritis model in C57BL/6 mice. Arthritis Rheumatol. 2022;74:1139–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhang M, Hu W, Cai C, Wu Y, Li J, Dong S. Advanced application of stimuli-responsive drug delivery system for inflammatory arthritis treatment. Mater Today Bio. 2022;14: 100223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Li C, Zheng X, Hu M, Jia M, Jin R, Nie Y. Recent progress in therapeutic strategies and biomimetic nanomedicines for rheumatoid arthritis treatment. Expert Opin Drug Deliv. 2022;19:883–98.

    Article  CAS  PubMed  Google Scholar 

  39. Mohammadinejad R, Moosavi MA, Tavakol S, Vardar DO, Hosseini A, Rahmati M, et al. Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles. Autophagy. 2019;15:4–33.

    Article  CAS  PubMed  Google Scholar 

  40. Means N, Elechalawar CK, Chen WR, Bhattacharya R, Mukherjee P. Revealing macropinocytosis using nanoparticles. Mol Aspects Med. 2022;83: 100993.

    Article  PubMed  Google Scholar 

  41. Zeng C, Feng Y, Wang W, Zhou F, Liao F, Liu Y, et al. The size-dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway. Environ Toxicol. 2018;33:1221–8.

    Article  CAS  PubMed  Google Scholar 

  42. Guo X, Wu Z, Li W, Wang Z, Li Q, Kong F, et al. Appropriate size of magnetic nanoparticles for various bioapplications in cancer diagnostics and therapy. ACS Appl Mater Interfaces. 2016;8:3092–106.

    Article  CAS  PubMed  Google Scholar 

  43. Park MV, Neigh AM, Vermeulen JP, de la Fonteyne LJ, Verharen HW, Briede JJ, et al. The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles. Biomaterials. 2011;32:9810–7.

    Article  CAS  PubMed  Google Scholar 

  44. Liu Y, Wang Z, Liu Y, Zhu G, Jacobson O, Fu X, et al. Suppressing nanoparticle-mononuclear phagocyte system interactions of two-dimensional gold nanorings for improved tumor accumulation and photothermal ablation of tumors. ACS Nano. 2017;11:10539–48.

    Article  CAS  PubMed  Google Scholar 

  45. Tsoi KM, MacParland SA, Ma XZ, Spetzler VN, Echeverri J, Ouyang B, et al. Mechanism of hard-nanomaterial clearance by the liver. Nat Mater. 2016;15:1212–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Special Funding for the Construction of Innovative Provinces in Hunan (Grant Nos. 2019SK2301), the Science and Technology Innovation Program of Hunan Province (Grant Nos. 2022RC1211), the China National Postdoctoral Program for Innovative Talents (Grant Nos. BX2021383), the Central South University Innovation-Driven Research Programme (Grant Nos. 2023CXQD001), the Hunan Province Natural Science Foundation of China (Grant No. 2023JJ10094), and the Hunan Provincial Innovation Foundation for Postgraduate (Grant Nos. 2021zzts0342, 2022ZZTS0239). We especially thank Professor Fu-Bin Li (Shanghai Jiao Tong University) for providing T cell receptor (TCR)-transgenic KRN mice.

Author information

Authors and Affiliations

  1. Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Ze-Hui He, Jing-Tao Zou, Xia Chen, Jiang-Shan Gong, Ya Chen, Ling Jin, Yi-Wei Liu, Shan-Shan Rao, Hao Yin, Yi-Juan Tan, Zun Wang, Wei Du, Hong-Ming Li, Yu-Xuan Qian, Zhen-Xing Wang, Yi-Yi Wang, Teng-Fei Wan, Yi Luo, Hao Zhu, Chun-Yuan Chen & Hui Xie

  2. Hunan Key Laboratory of Angmedicine, Changsha, Hunan, China

    Ze-Hui He, Jing-Tao Zou, Jiang-Shan Gong, Ya Chen, Ling Jin, Yi-Wei Liu, Shan-Shan Rao, Hao Yin, Yi-Juan Tan, Hong-Ming Li, Yu-Xuan Qian, Zhen-Xing Wang, Yi-Yi Wang, Teng-Fei Wan, Yi Luo, Hao Zhu, Chun-Yuan Chen & Hui Xie

  3. Angmedicine Research Center, Central south university, Changsha, China

    Ze-Hui He, Jing-Tao Zou, Jiang-Shan Gong, Ya Chen, Ling Jin, Yi-Wei Liu, Shan-Shan Rao, Hao Yin, Yi-Juan Tan, Hong-Ming Li, Yu-Xuan Qian, Zhen-Xing Wang, Yi-Yi Wang, Teng-Fei Wan, Yi Luo, Hao Zhu, Chun-Yuan Chen & Hui Xie

  4. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Xia Chen, Shan-Shan Rao, Zhen-Xing Wang, Chun-Yuan Chen & Hui Xie

  5. Xiangya School of Nursing, Central South University, Changsha, Hunan, China

    Zun Wang

  6. Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Wei Du

Authors
  1. Ze-Hui He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jing-Tao Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xia Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiang-Shan Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ya Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ling Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yi-Wei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shan-Shan Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hao Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yi-Juan Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Wei Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hong-Ming Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yu-Xuan Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Zhen-Xing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yi-Yi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Teng-Fei Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Yi Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Hao Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Chun-Yuan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Hui Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HX, C-YC, and Z-HH designed this study. Z-HH and C-YC wrote the manuscript. Z-HH, J-TZ, XC, J-SG, YC, LJ, Y-WL, WD, H-ML, Y-XQ, Y-YW, T-FW, HZ, and YL, did the experiments or/and analyzed the data. Z-HH and C-YC prepared the figures. S-SR, YH, Y-JT, Z-XW, and ZW provided technical support. All authors read and approved the manuscript.

Corresponding authors

Correspondence to Chun-Yuan Chen or Hui Xie.

Ethics declarations

Conflict of interest

No conflict of interest.

Ethics approval

All animal experiments in this study were approved by the Ethical Review Board at Xiangya Hospital of Central South University (no. 202009015). Animal care and all experimental procedures were conducted in accordance with the Department of Laboratory Animals of Central South University.

Consent to publish

Not applicable.

Consent to participate

Not applicable.

Additional information

Responsible Editor: Jason J. McDougall.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 506 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

He, ZH., Zou, JT., Chen, X. et al. Ångstrom-scale silver particles ameliorate collagen-induced and K/BxN-transfer arthritis in mice via the suppression of inflammation and osteoclastogenesis. Inflamm. Res. 72, 2053–2072 (2023). https://doi.org/10.1007/s00011-023-01778-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-023-01778-0

Keywords

Search

Navigation