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Natural product curcumin-based coordination nanoparticles for treating osteoarthritis via targeting Nrf2 and blocking NLRP3 inflammasome

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Abstract

Oxidative stress leads to chondrocyte apoptosis and extracellular matrix (ECM) degradation, thus contributing to the pathogenesis of osteoarthritis (OA). Herein, curcumin with remarkable antioxidant and anti-inflammatory activities has been employed as an organic ligand to coordinate ferric ions for enhancing the water-solubility and biocompatibility of natural product curcumin. The obtained iron-curcumin-based coordination nanoparticles (Fe-Cur NPs) exhibit great water-solubility and efficient reactive oxygen/nitrogen species (ROS/RNS) scavenging ability. In vitro chondrocyte evaluation experiments indicated that the intracellular ROS/RNS induced by interleukin 1β (IL-1β) could be efficiently scavenged by these Fe-Cur NPs and oxidative-stress-induced cell death could be preserved as well. In addition, post intra-articular (i.a.) injection into OA rat joints, Fe-Cur NPs could greatly inhibit OA progression via activating the nuclear factor-erythroid 2 related factor-2 (Nrf2) and inhibiting nod-like receptor protein-3 (NLRP3) inflammasome activation in primary rat chondrocytes, as well as decrease the production of matrix degrading proteases and other inflammatory mediators. The efficient antioxidation and anti-inflammation performance of Fe-Cur NPs endow them as a promising nanoplatform for treatment of various inflammatory diseases, and more detailed researches will be conducted in the future.

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References

  1. Chen, D.; Shen, J.; Zhao, W. W.; Wang, T. Y.; Han, L.; Hamilton, J.; Im, H. J. Osteoarthritis: Toward a comprehensive understanding of pathological mechanism. Bone Res. 2017, 5, 16044.

    Article  CAS  Google Scholar 

  2. Hunter, D. J.; Bierma-Zeinstra, S. Osteoarthritis. Lancet 2019, 393, 1745–1759.

    Article  CAS  Google Scholar 

  3. Morales-Ivorra, I.; Romera-Baures, M.; Roman-Viñas, B.; Serra-Majem, L. Osteoarthritis and the mediterranean diet: A systematic review. Nutrients 2018, 10, 1030.

    Article  Google Scholar 

  4. Loeser, R.; Collins, J. A.; Diekman, B. O. Ageing and the pathogenesis of osteoarthritis. Nat. Rev. Rheumatol. 2016, 12, 412–420.

    Article  CAS  Google Scholar 

  5. Pan, X. X.; Chen, T. T.; Zhang, Z. J.; Chen, X. W.; Chen, C. S.; Chen, L.; Wang, X. Y.; Ying, X. Z. Activation of Nrf2/HO-1 signal with myricetin for attenuating ECM degradation in human chondrocytes and ameliorating the murine osteoarthritis. Int. Immunopharmacol. 2019, 75, 105742.

    Article  CAS  Google Scholar 

  6. Wojdasiewicz, P.; Poniatowski, Ł. A.; Szukiewicz, D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediat. Inflamm. 2014, 2014, 561459.

    Article  Google Scholar 

  7. Loeser, R. F. Aging and osteoarthritis: The role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthr. Cartilage 2009, 17, 971–979.

    Article  CAS  Google Scholar 

  8. Li, D.; Wang, W. C.; Xie, G. R. Reactive oxygen species: The 2-edged sword of osteoarthritis. Am. J. Med. Sci. 2012, 344, 486–490.

    Article  Google Scholar 

  9. Kang, C. S.; Jung, E.; Hyeon, H.; Seon, S.; Lee, D. Acid-activatable polymeric curcumin nanoparticles as therapeutic agents for osteoarthritis. Nanomedicine:Nanotechnol., Biol. Med. 2020, 23, 102104.

    Article  CAS  Google Scholar 

  10. Bannuru, R. R.; Osani, M. C.; Al-Eid, F.; Wang, C. C. Efficacy of curcumin and Boswellia for knee osteoarthritis: Systematic review and meta-analysis. Semin. Arthritis Rheum. 2018, 48, 416–429.

    Article  CAS  Google Scholar 

  11. Shi, S. R.; Tian, T. R.; Li, Y. J.; Xiao, D. X.; Zhang, T.; Gong, P.; Lin, Y. F. Tetrahedral framework nucleic acid inhibits chondrocyte apoptosis and oxidative stress through activation of autophagy. ACS Appl. Mater. Interfaces 2020, 12, 56782–56791.

    Article  CAS  Google Scholar 

  12. Liang, R. M.; Zhao, J. M.; Li, B.; Cai, P. A.; Loh, X. J.; Xu, C. H.; Chen, P.; Kai, D.; Zheng, L. Implantable and degradable antioxidant poly(ε-caprolactone)-lignin nanofiber membrane for effective osteoarthritis treatment. Biomaterials 2020, 230, 119601.

    Article  CAS  Google Scholar 

  13. Zhu, D. C.; Wang, Y. H.; Lin, J. H.; Miao, Z. M.; Xu, J. J.; Wu, Y. S. Maltol inhibits the progression of osteoarthritis via the nuclear factor-erythroid 2-related factor-2/heme oxygenase-1 signal pathway in vitro and in vivo. Food Funct. 2021, 12, 1327–1337.

    Article  CAS  Google Scholar 

  14. Lee, D. Y.; Park, Y. J.; Song, M. G.; Kim, D. R.; Zada, S.; Kim, D. H. Cytoprotective effects of delphinidin for human chondrocytes against oxidative stress through activation of autophagy. Antioxidants 2020, 9, 83.

    Article  CAS  Google Scholar 

  15. Ansari, M. Y.; Ahmad, N.; Haqqi, T. M. Oxidative stress and inflammation in osteoarthritis pathogenesis: Role of polyphenols. Biomed. Pharmacother. 2020, 129, 110452.

    Article  CAS  Google Scholar 

  16. Cuadrado, A.; Rojo, A. I.; Wells, G.; Hayes, J. D.; Cousin, S. P.; Rumsey, W. L.; Attucks, O. C.; Franklin, S.; Levonen, A. L.; Kensler, T. W. et al. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat. Rev. Drug Discov. 2019, 18, 295–317.

    Article  CAS  Google Scholar 

  17. Bollong, M. J.; Lee, G.; Coukos, J. S.; Yun, H.; Zambaldo, C.; Chang, J. W.; Chin, E. N.; Ahmad, I.; Chatterjee, A. K. et al. A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling. Nature 2018, 562, 600–604.

    Article  CAS  Google Scholar 

  18. Bambouskova, M.; Gorvel, L.; Lampropoulou, V.; Sergushichev, A.; Loginicheva, E.; Johnson, K.; Korenfeld, D.; Mathyer, M. E.; Kim, H.; Huang, L. H. et al. Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis. Nature 2018, 556, 501–504.

    Article  CAS  Google Scholar 

  19. Nguyen, T.; Sherratt, P. J.; Huang, H. C.; Yang, C. S.; Pickett, C. B. Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element. Degradation of Nrf2 by the 26 S proteasome. J. Biol. Chem. 2003, 278, 4536–4541.

    Article  CAS  Google Scholar 

  20. Tkachev, V. O.; Menshchikova, E. B.; Zenkov, N. K. Mechanism of the Nrf2/Keap1/ARE signaling system. Biochemistry 2011, 76, 407–422.

    CAS  Google Scholar 

  21. Poulet, B.; Beier, F. Targeting oxidative stress to reduce osteoarthritis. Arthritis Res. Ther. 2016, 18, 32.

    Article  Google Scholar 

  22. Zhang, X.; Zhang, J. H.; Chen, X. Y.; Hu, Q. H.; Wang, M. X.; Jin, R.; Zhang, Q. Y.; Wang, W.; Wang, R.; Kang, L. L. et al. Reactive oxygen species-induced TXNIP drives fructose-mediated hepatic inflammation and lipid accumulation through NLRP3 inflammasome activation. Antioxid. Redox Signaling 2015, 22, 848–870.

    Article  CAS  Google Scholar 

  23. Luo, J. F.; Shen, X. Y.; Lio, C. K.; Dai, Y.; Cheng, C. S.; Liu, J. X.; Yao, Y. D.; Yu, Y.; Xie, Y.; Luo, P. et al. Activation of Nrf2/HO-1 pathway by nardochinoid C inhibits inflammation and oxidative stress in lipopolysaccharide-stimulated macrophages. Front. Pharmacol. 2018, 9, 911.

    Article  Google Scholar 

  24. Choi, R. J.; Cheng, M. S.; Kim, Y. S. Desoxyrhapontigenin upregulates Nrf2-mediated heme oxygenase-1 expression in macrophages and inflammatory lung injury. Redox Biol. 2014, 2, 504–512.

    Article  Google Scholar 

  25. Rosillo, M. A.; Sánchez-Hidalgo, M.; González-Benjumea, A.; Fernández-Bolaños, J. G.; Lubberts, E.; Alarcón-de-la-Lastra, C. Preventive effects of dietary hydroxytyrosol acetate, an extra virgin olive oil polyphenol in murine collagen-induced arthritis. Mol. Nutr. Food Res. 2015, 59, 2537–2546.

    Article  CAS  Google Scholar 

  26. Wu, W. J.; Jia, W. W.; Liu, X. H.; Pan, L. L.; Zhang, Q. Y.; Yang, D.; Shen, X. Y.; Liu, L.; Zhu, Y. Z. S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathway. Redox Biol. 2016, 10, 157–167.

    Article  CAS  Google Scholar 

  27. McAllister, M. J.; Chemaly, M.; Eakin, A. J.; Gibson, D. S.; McGilligan, V. E. NLRP3 as a potentially novel biomarker for the management of osteoarthritis. Osteoarthritis Cartilage 2018, 66, 612–619.

    Article  Google Scholar 

  28. Scanzello, C. R.; Goldring, S. R. The role of synovitis in osteoarthritis pathogenesis. Bone 2012, 51, 249–257.

    Article  CAS  Google Scholar 

  29. Du, L.; Wang, J.; Chen, Y. B.; Li, X. Z.; Wang, L.; Li, Y.; Jin, X. P.; Gu, X. K.; Hao, M.; Zhu, X. et al. Novel biphenyl diester derivative AB-38b inhibits NLRP3 inflammasome through Nrf2 activation in diabetic nephropathy. Cell Biol. Toxicol. 2020, 36, 243–260.

    Article  CAS  Google Scholar 

  30. Zhong, X. Y.; Wang, X. W.; Zhan, G. T.; Tang, Y. A.; Yao, Y. Z.; Dong, Z. L.; Hou, L. Q.; Zhao, H.; Zeng, S. J.; Hu, J. et al. NaCeF4: Gd, Tb scintillator as an X-ray responsive photosensitizer for multimodal imaging-guided synchronous radio/radiodynamic therapy. Nano Lett. 2019, 19, 8234–8244.

    Article  CAS  Google Scholar 

  31. Ising, C.; Venegas, C.; Zhang, S. S.; Scheiblich, H.; Schmidt, S. V.; Vieira-Saecker, A.; Schwartz, S.; Albasset, S.; McManus, R. M.; Tejera, D. et al. NLRP3 inflammasome activation drives tau pathology. Nature 2019, 575, 669–673.

    Article  CAS  Google Scholar 

  32. Luo, B. B.; Huang, F.; Liu, Y. L.; Liang, Y. Y.; Wei, Z.; Ke, H. H.; Zeng, Z. Y.; Huang, W. Q.; He, Y. NLRP3 inflammasome as a molecular marker in diabetic cardiomyopathy. Front. Physiol. 2017, 8, 519.

    Article  Google Scholar 

  33. Martinon, F.; Tschopp, J. Inflammatory caspases and inflammasomes: Master switches of inflammation. Cell Death Differ. 2007, 14, 10–22.

    Article  CAS  Google Scholar 

  34. Zheng, S. C.; Zhu, X. X.; Xue, Y.; Zhang, L. H.; Zou, H. J.; Qiu, J. H.; Liu, Q. Role of the NLRP3 inflammasome in the transient release of IL-1β induced by monosodium urate crystals in human fibroblast-like synoviocytes. J. Inflamm. 2015, 12, 30.

    Article  Google Scholar 

  35. Samir, P.; Kesavardhana, S.; Patmore, D. M.; Gingras, S.; Malireddi, R. K. S.; Karki, R.; Guy, C. S.; Briard, B.; Place, D. E.; Bhattacharya, A. et al. DDX3X acts as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome. Nature 2019, 573, 590–594.

    Article  CAS  Google Scholar 

  36. Zhou, J. T.; Zhao, Y. N.; Wu, G. W.; Lin, B. B.; Li, Z. F.; Liu, X. X. Differential miRNAomics of the synovial membrane in knee osteoarthritis induced by bilateral anterior cruciate ligament transection in rats. Mol. Med. Rep. 2018, 18, 4051–4057.

    CAS  Google Scholar 

  37. Vaamonde-García, C.; Loureiro, J.; Valcárcel-Ares, M. N.; Riveiro-Naveira, R. R.; Ramil-Gómez, O.; Hermida-Carballo, L.; Centeno, A.; Meijide-Failde, R.; Blanco, F. J.; López-Armada, M. J. The mitochondrial inhibitor oligomycin induces an inflammatory response in the rat knee joint. BMC Musculoskelet Disord. 2017, 18, 254.

    Article  Google Scholar 

  38. Cai, D. W.; Yin, S. S.; Yang, J.; Jiang, Q.; Cao, W. S. Histone deacetylase inhibition activates Nrf2 and protects against osteoarthritis. Arthritis Res. Ther. 2015, 17, 269.

    Article  Google Scholar 

  39. Shin, J. W.; Chun, K. S.; Kim, D. H.; Kim, S. J.; Kim, S. H.; Cho, N. C.; Na, H. K.; Surh, Y. J. Curcumin induces stabilization of Nrf2 protein through Keap1 cysteine modification. Biochem. Pharmacol. 2020, 173, 113820.

    Article  CAS  Google Scholar 

  40. Lu, Y.; Wu, S.; Xiang, B.; Li, L.; Lin, Y. Curcumin attenuates oxaliplatin-induced liver injury and oxidative stress by activating the Nrf2 pathway. Drug Des., Devel. Ther. 2020, 14, 73–85.

    Article  CAS  Google Scholar 

  41. Feng, K.; Ge, Y. W.; Chen, Z. X.; Li, X. D.; Liu, Z. Q.; Li, X. L.; Li, H.; Tang, T. T.; Yang, F.; Wang, X. Q. Curcumin inhibits the PERK-eIF2 α-CHOP pathway through promoting SIRT1 expression in oxidative stress-induced rat chondrocytes and ameliorates osteoarthritis progression in a rat model. Oxid. Med. Cell. Longev. 2019, 2019, 8574386.

    Article  Google Scholar 

  42. Zhang, Z.; Leong, D. J.; Xu, L.; He, Z. Y.; Wang, A.; Navati, M.; Kim, S. J.; Hirsh, D. M.; Hardin, J. A.; Cobelli, N. J. et al. Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model. Arthritis Res. Ther. 2016, 18, 128.

    Article  Google Scholar 

  43. Freigang, S.; Ampenberger, F.; Spohn, G.; Heer, S.; Shamshiev, A. T.; Kisielow, J.; Hersberger, M.; Yamamoto, M.; Bachmann, M. F.; Kopf, M. Nrf2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis. Eur. J. Immunol. 2011, 41, 2040–2051.

    Article  CAS  Google Scholar 

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Acknowledgements

This research was supported by the National Research Program of China (No. 2016YFA0201200), the National Natural Science Foundation of China (Nos. U20A20254 and 52072253), the China Postdoctoral Science Foundation (No. 2021TQ0229), the Collaborative Innovation Center of Suzhou Nano Science and Technology, the Preponderant Discipline Supporting Project of the Second Affiliated Hospital of Soochow University (No. XKTJXK202003), the Suzhou Special Foundation for the Key Diseases Diagnosis and Treatment (Nos. LCZX201904 and LCZX201708).

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  1. Zhiqiang Zhou, Fei Gong, Peng Zhang, and Xiaotong Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, China

    Zhiqiang Zhou, Peng Zhang, Xiang Gao & Xiaozhong Zhou

  2. Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, 215123, China

    Fei Gong, Rui Zhang & Liang Cheng

  3. Department of Hepatology and Gastroenterology, The Affiliated Infectious Hospital of Soochow University, Suzhou, 215007, China

    Xiaotong Wang

  4. Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, China

    Wei Xia

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  1. Zhiqiang Zhou
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  2. Fei Gong
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  3. Peng Zhang
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Correspondence to Fei Gong, Xiaozhong Zhou or Liang Cheng.

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Natural product curcumin-based coordination nanoparticles for treating osteoarthritis via targeting Nrf2 and blocking NLRP3 inflammasome

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Zhou, Z., Gong, F., Zhang, P. et al. Natural product curcumin-based coordination nanoparticles for treating osteoarthritis via targeting Nrf2 and blocking NLRP3 inflammasome. Nano Res. 15, 3338–3345 (2022). https://doi.org/10.1007/s12274-021-3864-3

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