Journal Home > Volume 15 , Issue 4
Nano Research 2022, 15(4): 3338-3345 https://doi.org/10.1007/s12274-021-3864-3
Research Article | Issue | Published: 28 October 2021

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

Show Author's Information Zhiqiang Zhou1,§,  Fei Gong2,§( ),  Peng Zhang1,§,  Xiaotong Wang3,§,  Rui Zhang2,  Wei Xia4,  Xiang Gao1,  Xiaozhong Zhou1( ),  Liang Cheng2( )
Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China
Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China
Department of Hepatology and Gastroenterology, The Affiliated Infectious Hospital of Soochow University, Suzhou 215007, China
Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China

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

Keywords:
osteoarthritis, iron-curcumin-based coordination nanoparticles (Fe-Cur NPs), reactive oxygen/nitrogen species (ROS/RNS) scavenging ability, antioxidation and anti-inflammation performance, signaling pathway
Topics:
Nanoparticles
Cite this article:
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 Research, 2022, 15(4): 3338-3345. https://doi.org/10.1007/s12274-021-3864-3
Download citation
EndNote(RIS)
BibTeX

908

Views

162

Downloads

Citations

22

Crossref

24

WoS

22

Scopus

2

CSCD

Abstract Full text Electronic supplementary material About this article

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.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

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

Show Author's information Zhiqiang Zhou1,§, Fei Gong2,§( ), Peng Zhang1,§, Xiaotong Wang3,§, Rui Zhang2, Wei Xia4, Xiang Gao1, Xiaozhong Zhou1( ), Liang Cheng2( )
Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China
Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China
Department of Hepatology and Gastroenterology, The Affiliated Infectious Hospital of Soochow University, Suzhou 215007, China
Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China

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

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.

Keywords: osteoarthritis, iron-curcumin-based coordination nanoparticles (Fe-Cur NPs), reactive oxygen/nitrogen species (ROS/RNS) scavenging ability, antioxidation and anti-inflammation performance, signaling pathway

References(43)

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.
DOI Google Scholar
2

Hunter, D. J.; Bierma-Zeinstra, S. Osteoarthritis. Lancet 2019, 393, 1745–1759.
DOI 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.
DOI Google Scholar
4

Loeser, R.; Collins, J. A.; Diekman, B. O. Ageing and the pathogenesis of osteoarthritis. Nat. Rev. Rheumatol. 2016, 12, 412–420.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI Google Scholar
21

Poulet, B.; Beier, F. Targeting oxidative stress to reduce osteoarthritis. Arthritis Res. Ther. 2016, 18, 32.
DOI 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.
DOI 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.
DOI Google Scholar
24

Choi, R. J.; Cheng, M. S.; Kim, Y. S. Desoxyrhapontigenin up-regulates Nrf2-mediated heme oxygenase-1 expression in macrophages and inflammatory lung injury. Redox Biol. 2014, 2, 504–512.
DOI 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.
DOI 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.
DOI 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, 26, 612–619.
DOI Google Scholar
28

Scanzello, C. R.; Goldring, S. R. The role of synovitis in osteoarthritis pathogenesis. Bone 2012, 51, 249–257.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI Google Scholar
33

Martinon, F.; Tschopp, J. Inflammatory caspases and inflammasomes: Master switches of inflammation. Cell Death Differ. 2007, 14, 10–22.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI 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.
DOI Google Scholar
File
12274_2021_3864_MOESM1_ESM.pdf (557.9 KB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 24 April 2021
Revised: 29 August 2021
Accepted: 04 September 2021
Published: 28 October 2021
Issue date: April 2022

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2021

Acknowledgements

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. XKTJ-XK202003), the Suzhou Special Foundation for the Key Diseases Diagnosis and Treatment (Nos. LCZX201904 and LCZX201708).

Return