Liposome/gold hybrid nanoparticle encoded with CoQ10 (LGNP-CoQ10) suppressed rheumatoid arthritis via STAT3/Th17 targeting

Jooyeon Jhun, Jeonghyeon Moon, Jaeyoon Ryu, Yonghee Shin, Seangyoun Lee, Keun-Hyung Cho, Taewook Kang, Mi-La Cho, Sung-Hwan Park, Jooyeon Jhun, Jeonghyeon Moon, Jaeyoon Ryu, Yonghee Shin, Seangyoun Lee, Keun-Hyung Cho, Taewook Kang, Mi-La Cho, Sung-Hwan Park

Abstract

Coenzyme Q10 (CoQ10), also known as ubiquinone, is a fat-soluble antioxidant. Although CoQ10 has not been approved as medication by the Food and Drug Administration, it is widely used in dietary supplements. Some studies have shown that CoQ10 has anti-inflammatory effects on various autoimmune disorders. In this study, we investigated the anti-inflammatory effects of liposome/gold hybrid nanoparticles encoded with CoQ10 (LGNP-CoQ10). Both CoQ10 and LGNP-CoQ10 were administered orally to mice with collagen-induced arthritis (CIA) for 10 weeks. The inflammation pathology of joint tissues of CIA mice was then analyzed using hematoxylin and eosin and Safranin O staining, as well as immunohistochemistry analysis. We obtained immunofluorescence staining images of spleen tissues using confocal microscopy. We found that pro-inflammatory cytokines were significantly decreased in LGNP-CoQ10 injected mice. Th17 cell and phosphorylated STAT3-expressed cell populations were also decreased in LGNP-CoQ10 injected mice. When human peripheral blood mononuclear cells (PBMCs) were treated with CoQ10 and LGNP-CoQ10, the IL-17 expression of PBMCs in the LGNP-CoQ10-treated group was significantly reduced. Together, these results suggest that LGNP-CoQ10 has therapeutic potential for the treatment of rheumatoid arthritis.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Formation of liposome/gold nanoparticles encoded…
Fig 1. Formation of liposome/gold nanoparticles encoded with CoQ10 (LGNP-CoQ10).
(A) Structure of the LGNP-CoQ10. (B and C) The cloudy color and ultraviolet-visible (UV-vis) absorbance of CoQ10, CoQ10 liposome, and CoQ10+gold liposome solutions are presented. (D) The morphology of liposomes that contained only CoQ10 and gold nanoparticles + CoQ10 was assessed by transmission electron microscopy (TEM). Scale bars = 50 nm.
Fig 2. Pathology scores of CoQ10 and…
Fig 2. Pathology scores of CoQ10 and LGNP-CoQ10-injected mice.
(A) The arthritis score and incidence of CIA mice in each group are shown. (B) Joint tissues of CIA mice were stained with hematoxylin and eosin as well as Safranin O. *P

Fig 3. Immunohistochemistry of joint tissues in…

Fig 3. Immunohistochemistry of joint tissues in vehicle-, CoQ10-, and LGNP-CoQ10-injected mice.

*P

Fig 3. Immunohistochemistry of joint tissues in vehicle-, CoQ10-, and LGNP-CoQ10-injected mice.
*P

Fig 4. Immunofluorescence of spleen tissues.

(A…

Fig 4. Immunofluorescence of spleen tissues.

(A and B) Th17 cells and phosphorylated STAT3 expression…

Fig 4. Immunofluorescence of spleen tissues.
(A and B) Th17 cells and phosphorylated STAT3 expression in the spleens of treatment with vehicle, CoQ10 and LGNP-CoQ10 were detected by confocal microscopy. *P

Fig 5. IL-17 levels were detected by…

Fig 5. IL-17 levels were detected by ELISA in human peripheral blood mononuclear cells (PBMC)…

Fig 5. IL-17 levels were detected by ELISA in human peripheral blood mononuclear cells (PBMC) in anti-CD3 conditions.
The isolated PBMC was seeded and treated the 0.5μM of CoQ10 and LGNP-CoQ10 for 3 days respectively. **P
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References
    1. Yap H.Y., Tee S.Z., Wong M.M., Chow S.K., Peh S.C., Teow S.Y., Pathogenic role of immune cells in rheumatoid arthritis: Implications in clinical treatment and biomarker development, Cells 7(10) (2018). 10.3390/cells7100161 - DOI - PMC - PubMed
    1. Lee Y.C., Kim S.H., Roh S.S., Choi H.Y., Seo Y.B., Suppressive effects of Chelidonium majus methanol extract in knee joint, regional lymph nodes, and spleen on collagen-induced arthritis in mice, J Ethnopharmacol 112(1) (2007) 40–48. 10.1016/j.jep.2007.01.033 - DOI - PubMed
    1. Komatsu N., Okamoto K., Sawa S., Nakashima T., Oh-hora M., Kodama T., et al., Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis, Nat Med 20(1) (2014) 62–68. 10.1038/nm.3432 - DOI - PubMed
    1. Mohammadi F.S., Aslani S., Mostafaei S., Jamshidi A., Riahi P., Mahmoudi M., Are genetic variations in IL-21-IL-23R-IL-17A cytokine axis involved in a pathogenic pathway of rheumatoid arthritis? Bayesian hierarchical meta-analysis, J Cell Physiol 234(10) (2019) 17159–17171. 10.1002/jcp.28495 - DOI - PubMed
    1. Dhaouadi T., Chahbi M., Haouami Y., Sfar I., Abdelmoula L., Ben Abdallah T., et al., IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis, PLoS One 13(3) (2018) e0194883 10.1371/journal.pone.0194883 - DOI - PMC - PubMed
Show all 32 references
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This research was supported by a grant from the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C1062). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Fig 3. Immunohistochemistry of joint tissues in…
Fig 3. Immunohistochemistry of joint tissues in vehicle-, CoQ10-, and LGNP-CoQ10-injected mice.
*P

Fig 4. Immunofluorescence of spleen tissues.

(A…

Fig 4. Immunofluorescence of spleen tissues.

(A and B) Th17 cells and phosphorylated STAT3 expression…

Fig 4. Immunofluorescence of spleen tissues.
(A and B) Th17 cells and phosphorylated STAT3 expression in the spleens of treatment with vehicle, CoQ10 and LGNP-CoQ10 were detected by confocal microscopy. *P

Fig 5. IL-17 levels were detected by…

Fig 5. IL-17 levels were detected by ELISA in human peripheral blood mononuclear cells (PBMC)…

Fig 5. IL-17 levels were detected by ELISA in human peripheral blood mononuclear cells (PBMC) in anti-CD3 conditions.
The isolated PBMC was seeded and treated the 0.5μM of CoQ10 and LGNP-CoQ10 for 3 days respectively. **P
Similar articles
Cited by
References
    1. Yap H.Y., Tee S.Z., Wong M.M., Chow S.K., Peh S.C., Teow S.Y., Pathogenic role of immune cells in rheumatoid arthritis: Implications in clinical treatment and biomarker development, Cells 7(10) (2018). 10.3390/cells7100161 - DOI - PMC - PubMed
    1. Lee Y.C., Kim S.H., Roh S.S., Choi H.Y., Seo Y.B., Suppressive effects of Chelidonium majus methanol extract in knee joint, regional lymph nodes, and spleen on collagen-induced arthritis in mice, J Ethnopharmacol 112(1) (2007) 40–48. 10.1016/j.jep.2007.01.033 - DOI - PubMed
    1. Komatsu N., Okamoto K., Sawa S., Nakashima T., Oh-hora M., Kodama T., et al., Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis, Nat Med 20(1) (2014) 62–68. 10.1038/nm.3432 - DOI - PubMed
    1. Mohammadi F.S., Aslani S., Mostafaei S., Jamshidi A., Riahi P., Mahmoudi M., Are genetic variations in IL-21-IL-23R-IL-17A cytokine axis involved in a pathogenic pathway of rheumatoid arthritis? Bayesian hierarchical meta-analysis, J Cell Physiol 234(10) (2019) 17159–17171. 10.1002/jcp.28495 - DOI - PubMed
    1. Dhaouadi T., Chahbi M., Haouami Y., Sfar I., Abdelmoula L., Ben Abdallah T., et al., IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis, PLoS One 13(3) (2018) e0194883 10.1371/journal.pone.0194883 - DOI - PMC - PubMed
Show all 32 references
Publication types
MeSH terms
Grant support
This research was supported by a grant from the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C1062). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Cite
Copy Download .nbib
Format: AMA APA MLA NLM

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The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

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Fig 4. Immunofluorescence of spleen tissues.
Fig 4. Immunofluorescence of spleen tissues.
(A and B) Th17 cells and phosphorylated STAT3 expression in the spleens of treatment with vehicle, CoQ10 and LGNP-CoQ10 were detected by confocal microscopy. *P

Fig 5. IL-17 levels were detected by…

Fig 5. IL-17 levels were detected by ELISA in human peripheral blood mononuclear cells (PBMC)…

Fig 5. IL-17 levels were detected by ELISA in human peripheral blood mononuclear cells (PBMC) in anti-CD3 conditions.
The isolated PBMC was seeded and treated the 0.5μM of CoQ10 and LGNP-CoQ10 for 3 days respectively. **P
Similar articles
Cited by
References
    1. Yap H.Y., Tee S.Z., Wong M.M., Chow S.K., Peh S.C., Teow S.Y., Pathogenic role of immune cells in rheumatoid arthritis: Implications in clinical treatment and biomarker development, Cells 7(10) (2018). 10.3390/cells7100161 - DOI - PMC - PubMed
    1. Lee Y.C., Kim S.H., Roh S.S., Choi H.Y., Seo Y.B., Suppressive effects of Chelidonium majus methanol extract in knee joint, regional lymph nodes, and spleen on collagen-induced arthritis in mice, J Ethnopharmacol 112(1) (2007) 40–48. 10.1016/j.jep.2007.01.033 - DOI - PubMed
    1. Komatsu N., Okamoto K., Sawa S., Nakashima T., Oh-hora M., Kodama T., et al., Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis, Nat Med 20(1) (2014) 62–68. 10.1038/nm.3432 - DOI - PubMed
    1. Mohammadi F.S., Aslani S., Mostafaei S., Jamshidi A., Riahi P., Mahmoudi M., Are genetic variations in IL-21-IL-23R-IL-17A cytokine axis involved in a pathogenic pathway of rheumatoid arthritis? Bayesian hierarchical meta-analysis, J Cell Physiol 234(10) (2019) 17159–17171. 10.1002/jcp.28495 - DOI - PubMed
    1. Dhaouadi T., Chahbi M., Haouami Y., Sfar I., Abdelmoula L., Ben Abdallah T., et al., IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis, PLoS One 13(3) (2018) e0194883 10.1371/journal.pone.0194883 - DOI - PMC - PubMed
Show all 32 references
Publication types
MeSH terms
Grant support
This research was supported by a grant from the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C1062). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Fig 5. IL-17 levels were detected by…
Fig 5. IL-17 levels were detected by ELISA in human peripheral blood mononuclear cells (PBMC) in anti-CD3 conditions.
The isolated PBMC was seeded and treated the 0.5μM of CoQ10 and LGNP-CoQ10 for 3 days respectively. **P

References

    1. Yap H.Y., Tee S.Z., Wong M.M., Chow S.K., Peh S.C., Teow S.Y., Pathogenic role of immune cells in rheumatoid arthritis: Implications in clinical treatment and biomarker development, Cells 7(10) (2018). 10.3390/cells7100161
    1. Lee Y.C., Kim S.H., Roh S.S., Choi H.Y., Seo Y.B., Suppressive effects of Chelidonium majus methanol extract in knee joint, regional lymph nodes, and spleen on collagen-induced arthritis in mice, J Ethnopharmacol 112(1) (2007) 40–48. 10.1016/j.jep.2007.01.033
    1. Komatsu N., Okamoto K., Sawa S., Nakashima T., Oh-hora M., Kodama T., et al., Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis, Nat Med 20(1) (2014) 62–68. 10.1038/nm.3432
    1. Mohammadi F.S., Aslani S., Mostafaei S., Jamshidi A., Riahi P., Mahmoudi M., Are genetic variations in IL-21-IL-23R-IL-17A cytokine axis involved in a pathogenic pathway of rheumatoid arthritis? Bayesian hierarchical meta-analysis, J Cell Physiol 234(10) (2019) 17159–17171. 10.1002/jcp.28495
    1. Dhaouadi T., Chahbi M., Haouami Y., Sfar I., Abdelmoula L., Ben Abdallah T., et al., IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis, PLoS One 13(3) (2018) e0194883 10.1371/journal.pone.0194883
    1. Weng L., Williams R.O., Vieira P.L., Screaton G., Feldmann M., Dazzi F., The therapeutic activity of low-dose irradiation on experimental arthritis depends on the induction of endogenous regulatory T cell activity, Ann Rheum Dis 69(8) (2010) 1519–1526. 10.1136/ard.2009.121111
    1. Agmo Hernandez V., Eriksson E.K., Edwards K., Ubiquinone-10 alters mechanical properties and increases stability of phospholipid membranes, Biochim Biophys Acta 1848(10 Pt A) (2015) 2233–2243. 10.1016/j.bbamem.2015.05.002
    1. Sarmiento A., Diaz-Castro J., Pulido-Moran M., Kajarabille N., Guisado R., Ochoa J.J., Coenzyme Q10 supplementation and exercise in healthy humans: A systematic review, Curr Drug Metab 17(4) (2016) 345–358. 10.2174/1389200216666151103115654
    1. Chen H.C., Huang C.C., Lin T.J., Hsu M.C., Hsu Y.J., Ubiquinol supplementation alters exercise induced fatigue by increasing lipid utilization in mice, Nutrients 11(11) (2019). 10.3390/nu11112550
    1. Sanbe A., Tanonaka K., Niwano Y., Takeo S., Improvement of cardiac function and myocardial energy metabolism of rats with chronic heart failure by long-term coenzyme Q10 treatment, J Pharmacol Exp Ther 269(1) (1994) 51–56.
    1. Al-Megrin W.A., Soliman D., Kassab R.B., Metwally D.M., Ahmed E.A.M., El-Khadragy M.F., Coenzyme Q10 activates the antioxidant machinery and inhibits the inflammatory and apoptotic cascades against lead acetate-induced renal injury in rats, Front Physiol 11 (2020) 64 10.3389/fphys.2020.00064
    1. El Agamy D.F., Naguib Y.M., CoQ10 ameliorates monosodium glutamate-induced alteration in detrusor activity and responsiveness in rats via anti-inflammatory, anti-oxidant and channel inhibiting mechanisms, BMC Urol 19(1) (2019) 103 10.1186/s12894-019-0534-9
    1. Abdollahzad H., Aghdashi M.A., Asghari Jafarabadi M., Alipour B., Effects of coenzyme Q10 supplementation on inflammatory cytokines (TNF-alpha, IL-6) and oxidative stress in rheumatoid arthritis patients: A randomized controlled trial, Arch Med Res 46(7) (2015) 527–533. 10.1016/j.arcmed.2015.08.006
    1. Bauerova K., Ponist S., Mihalova D., Drafi F., Kuncirova V., Utilization of adjuvant arthritis model for evaluation of new approaches in rheumatoid arthritis therapy focused on regulation of immune processes and oxidative stress, Interdiscip Toxicol 4(1) (2011) 33–39. 10.2478/v10102-011-0007-9
    1. Jhun J., Lee S., Kim S.Y., Na H.S., Kim E.K., Kim J.K., et al., Combination therapy with metformin and coenzyme Q10 in murine experimental autoimmune arthritis, Immunopharmacol Immunotoxicol 38(2) (2016) 103–112. 10.3109/08923973.2015.1122619
    1. Lee S.H., Park M.J., Lee S.H., Cho M.L., Coenzyme Q10 exerts anti-inflammatory activity and induces Treg in graft versus host disease, J Med Food 19(3) (2016) 238–244. 10.1089/jmf.2015.3535
    1. Jhun J., Lee S.H., Byun J.K., Jeong J.H., Kim E.K., Lee J., et al., Coenzyme Q10 suppresses Th17 cells and osteoclast differentiation and ameliorates experimental autoimmune arthritis mice, Immunol Lett 166(2) (2015) 92–102. 10.1016/j.imlet.2015.05.012
    1. Lee S.Y., Lee S.H., Yang E.J., Kim J.K., Kim E.K., Jung K., et al., Coenzyme Q10 inhibits Th17 and STAT3 signaling pathways to ameliorate colitis in mice, J Med Food 20(9) (2017) 821–829. 10.1089/jmf.2016.3859
    1. Takekawa Y., Sato Y., Yamaki Y., Imai M., Noto K., Sumi M., et al., An approach to improve intestinal absorption of poorly absorbed water-insoluble components via Niemann–Pick C1-like 1, Biol Pharm Bull 39(3) (2016) 301–307. 10.1248/bpb.b15-00359
    1. Rengan A.K., Bukhari A.B., Pradhan A., Malhotra R., Banerjee R., Srivastava R., et al., In vivo analysis of biodegradable liposome gold nanoparticles as efficient agents for photothermal therapy of cancer, Nano Lett 15(2) (2015) 842–848. 10.1021/nl5045378
    1. Lajunen T., Viitala L., Kontturi L.S., Laaksonen T., Liang H., Vuorimaa-Laukkanen E., et al., Light induced cytosolic drug delivery from liposomes with gold nanoparticles, J Control Release 203 (2015) 85–98. 10.1016/j.jconrel.2015.02.028
    1. Liang R., Xie J., Li J., Wang K., Liu L., Gao Y., et al., Liposomes-coated gold nanocages with antigens and adjuvants targeted delivery to dendritic cells for enhancing antitumor immune response, Biomaterials 149 (2017) 41–50. 10.1016/j.biomaterials.2017.09.029
    1. Xu N., Li J., Gao Y., Zhou N., Ma Q., Wu M., et al., Apoptotic cell-mimicking gold nanocages loaded with LXR agonist for attenuating the progression of murine systemic lupus erythematosus, Biomaterials 197 (2019) 380–392. 10.1016/j.biomaterials.2019.01.034
    1. Lee J.H., Shin Y., Lee W., Whang K., Kim D., Lee L.P., et al., General and programmable synthesis of hybrid liposome/metal nanoparticles, Sci Adv 2(12) (2016) e1601838 10.1126/sciadv.1601838
    1. Camps M., Ruckle T., Ji H., Ardissone V., Rintelen F., Shaw J., et al., Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis, Nat Med 11(9) (2005) 936–943. 10.1038/nm1284
    1. Liu S., Liu X., Xiong H., Wang W., Liu Y., Yin L., et al., CXCL13/CXCR5 signaling contributes to diabetes-induced tactile allodynia via activating pERK, pSTAT3, pAKT pathways and pro-inflammatory cytokines production in the spinal cord of male mice, Brain Behav Immun 80 (2019) 711–724. 10.1016/j.bbi.2019.05.020
    1. Weber C., Bysted A., Holmer G., Coenzyme Q10 in the diet: Daily intake and relative bioavailability, Mol Aspects Med 18 Suppl (1997) S251–S254.
    1. Song Y., Han J., Feng R., Wang M., Tian Q., Zhang T., et al., The 12-3-12 cationic gemini surfactant as a novel gastrointestinal bioadhesive material for improving the oral bioavailability of coenzyme Q10 naked nanocrystals, Drug Dev Ind Pharm 42(12) (2016) 2044–2054. 10.1080/03639045.2016.1195399
    1. Ochiai A., Itagaki S., Kurokawa T., Kobayashi M., Hirano T., Iseki K., Improvement in intestinal coenzyme q10 absorption by food intake, Yakugaku Zasshi 127(8) (2007) 1251–1254. 10.1248/yakushi.127.1251
    1. Lee Youngjae, Jang Jungwoo, Yoon Jinho, Choi Jeong-Woo, Choi Inhee, Kang Taewook. Phase transfer-driven rapid and complete ligand exchange for molecular assembly of phospholipid bilayers on aqueous gold nanocrystals. Chem Commun (Camb) 55(22) (2019) 3195–3198. 10.1039/c8cc10037c
    1. Lee Jin-Ho, Shin Yonghee, Lee Wooju, Whang Keumrai, Kim Dongchoul, Lee Luke P., et al., General and programmable synthesis of hybrid liposome/metal nanoparticles. Sci Adv 2(12) (2016) e1601838 10.1126/sciadv.1601838
    1. Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell(5) (2011) 772–84. 10.1016/j.cell.2011.07.033

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