Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Characterization and Immunogenicity of Recombinant A. flavus Uox Modified by Co/EDTA Carbon Dots

Author(s): Hai-Ling Li, Xiu-Feng Gao*, Jing-Ji Li, Ming-Xia Wan, Guo-Qi Zhang and Yong-Sheng Li*

Volume 25, Issue 2, 2024

Published on: 22 June, 2023

Page: [230 - 246] Pages: 17

DOI: 10.2174/1389201024666230519144615

Price: $65

Abstract

Background: Uricase (Uox) is a major drug in gout and a supplementary drug in cancer treatment. Because allergic reactions caused by Uox limit its clinical application,10% Co/EDTA was used to chemically modify Uox from A. flavus to reduce its immunogenicity.

Methods: The immunogenicity of Uox and 10% Co/EDTA-Uox was examined by determining the antibody titer and concentration of IL-2, IL-6, IL-10, and TNF-β in quail and rat serum. Moreover, we examined the pharmacokinetics of 10% Co/EDTA-Uox in rats and acute toxicity in mice.

Results: The concentration of UA decreased from 771.85 ± 180.99 to 299.47 ± 20.37 μmoL/L (p<0.01) in the hyperuricemia model of quails injected by 10% Co/EDTA-Uox. Two-way immuno- diffusion electrophoresis revealed that 10% Co/EDTA-Uox did not produce antibody, whereas the antibody titer against Uox was 1:16. The concentrations of four cytokines in the 10% Co/EDTA-Uox group were significantly lower than in Uox group (p < 0.01); The titer of IgG and IgM against 10% Co/EDTA-Uox was significantly lower than that against Uox at different serum dilutions (p < 0.0001). The pharmacokinetic data indicated that the half-life time of 10% Co/EDTA- Uox (69.315 h) was significantly longer than that of Uox (13.4 h) (p<0.01). The tissue section of the liver, heart, kidney, and spleen revealed no toxicity in Uox and 10% Co/EDTA- Uox groups.

Conclusion: 10% Co/EDTA-Uox possesses little immunogenicity, a long half-life time, and a highly efficient degradation of UA.

Keywords: UA, hyperuricemia, Uox, Co/EDTA-Uox, cytotoxicity, immunogenicity.

« Previous
Graphical Abstract

[1]
Li, Z. Phylogenetic articulation of uric acid evolution in mammals and how it informs a therapeutic uriase. Mol. Biol. Evol., 2021, 39(1), 1-8.
[http://dx.doi.org/10.1093/molbev/msab312]
[2]
Perez-Ruiz, F.M.D. Gout. Rheum. Dis. Clin. North Am., 2019, 4(45), 583-591.
[3]
Dehlin, M.; Drivelegka, P.; Sigurdardottir, V.; Svärd, A.; Jacobsson, L.T.H. Incidence and prevalence of gout in Western Sweden. Arthritis Res. Ther., 2016, 18(1), 164-170.
[http://dx.doi.org/10.1186/s13075-016-1062-6] [PMID: 27412614]
[4]
Rai, S.K.; Aviña-Zubieta, J.A.; McCormick, N. The rising prevalence and incidence of gout in British Columbia, Canada: Population-based trends from 2000 to 2012. Semin. Arthritis Rheum., 2017, 46, 451-456.
[5]
Kim, J.W.; Kwak, S.G.; Lee, H.; Kim, S.K.; Choe, J.Y.; Park, S.H. Prevalence and incidence of gout in Korea: Data from the national health claims database 2007–2015. Rheumatol. Int., 2017, 37(9), 1499-1506.
[http://dx.doi.org/10.1007/s00296-017-3768-4] [PMID: 28676911]
[6]
Kuo, C.F.; Grainge, M.J.; Mallen, C.; Zhang, W.; Doherty, M. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann. Rheum. Dis., 2015, 74(4), 661-667.
[http://dx.doi.org/10.1136/annrheumdis-2013-204463] [PMID: 24431399]
[7]
Zobbe, K.; Prieto-Alhambra, D.; Cordtz, R.; Højgaard, P.; Hindrup, J.S.; Kristensen, L.E.; Dreyer, L. Secular trends in the incidence and prevalence of gout in Denmark from 1995 to 2015: a nationwide register-based study. Rheumatology (Oxford), 2019, 58(5), 836-839.
[http://dx.doi.org/10.1093/rheumatology/key390] [PMID: 30590724]
[8]
Chen-Xu, M.; Yokose, C.; Rai, S.K.; Pillinger, M.H.; Choi, H.K. Contemporary prevalence of gout and hyperuricemia in the United States and decadal trends: The National Health and Nutrition Examination Survey, 2007–2016. Arthritis Rheumatol., 2019, 71(6), 991-999.
[http://dx.doi.org/10.1002/art.40807] [PMID: 30618180]
[9]
Drivelegka, P.; Sigurdardottir, V.; Svärd, A.; Jacobsson, L.T.H.; Dehlin, M. Comorbidity in gout at the time of first diagnosis: sex differences that may have implications for dosing of urate lowering therapy. Arthritis Res. Ther., 2018, 20(1), 108-119.
[http://dx.doi.org/10.1186/s13075-018-1596-x] [PMID: 29855389]
[10]
Vitart, V.; Rudan, I.; Hayward, C.; Gray, N.K.; Floyd, J.; Palmer, C.N.A.; Knott, S.A.; Kolcic, I.; Polasek, O.; Graessler, J.; Wilson, J.F.; Marinaki, A.; Riches, P.L.; Shu, X.; Janicijevic, B.; Smolej-Narancic, N.; Gorgoni, B.; Morgan, J.; Campbell, S.; Biloglav, Z.; Barac-Lauc, L.; Pericic, M.; Klaric, I.M.; Zgaga, L.; Skaric-Juric, T.; Wild, S.H.; Richardson, W.A.; Hohenstein, P.; Kimber, C.H.; Tenesa, A.; Donnelly, L.A.; Fairbanks, L.D.; Aringer, M.; McKeigue, P.M.; Ralston, S.H.; Morris, A.D.; Rudan, P.; Hastie, N.D.; Campbell, H.; Wright, A.F. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat. Genet., 2008, 40(4), 437-442.
[http://dx.doi.org/10.1038/ng.106] [PMID: 18327257]
[11]
Enomoto, A.; Kimura, H.; Chairoungdua, A.; Shigeta, Y.; Jutabha, P.; Ho Cha, S.; Hosoyamada, M.; Takeda, M.; Sekine, T.; Igarashi, T.; Matsuo, H.; Kikuchi, Y.; Oda, T.; Ichida, K.; Hosoya, T.; Shimokata, K.; Niwa, T.; Kanai, Y.; Endou, H. Molecular identification of a renal urate–anion exchanger that regulates blood urate levels. Nature, 2002, 417(6887), 447-452.
[http://dx.doi.org/10.1038/nature742] [PMID: 12024214]
[12]
Ekaratanawong, S.; Anzai, N.; Jutabha, P. Human organic anion transporter 4 is a renal apical organic anion/dicarboxylate exchanger in the proximal tubules. J. Pharmacol. Sci., 2004, 94, 297-304.
[13]
Eraly, S.A.; Vallon, V.; Rieg, T. Multiple organic anion transporters contribute to net renal excretion of uric acid. Physiol. Genomics, 2008, 33, 180-192.
[http://dx.doi.org/10.1152/physiolgenomics.00207.2007]
[14]
Chhana, A.; Pool, B.; Wei, Y.; Choi, A.; Gao, R.; Munro, J.; Cornish, J.; Dalbeth, N. Human cartilage homogenates influence the crystallization of monosodium urate and inflammatory response to monosodium urate crystals: A potential link between osteoarthritis and gout. Arthritis Rheumatol., 2019, 71(12), 2090-2099.
[http://dx.doi.org/10.1002/art.41038] [PMID: 31297987]
[15]
Li, H.; Huo, J.; Sun, D.; Guo, Y.; Jiang, L.; Zhang, H.; Shi, X.; Zhao, Z.; Zhou, J.; Hu, C.; Zhang, C. Determination of PEGylation homogeneity of polyethylene glycol‐modified canine uricase. Electrophoresis, 2021, 42(6), 693-699.
[http://dx.doi.org/10.1002/elps.202000268] [PMID: 33247595]
[16]
Nyborg, A.C.; Ward, C.; Zacco, A.; Chacko, B.; Grinberg, L.; Geoghegan, J.C.; Bean, R.; Wendeler, M.; Bartnik, F.; O’Connor, E.; Gruia, F.; Iyer, V.; Feng, H.; Roy, V.; Berge, M.; Miner, J.N.; Wilson, D.M.; Zhou, D.; Nicholson, S.; Wilker, C.; Wu, C.Y.; Wilson, S.; Jermutus, L.; Wu, H.; Owen, D.A.; Osbourn, J.; Coats, S.; Baca, M.A. Therapeutic uricase with reduced immunogenicity risk and improved development properties. PLoS One, 2016, 11(12), e0167935.
[http://dx.doi.org/10.1371/journal.pone.0167935]
[17]
Bomalaski, M.J.S.; Goddard, D.H.; Grezlak, D.; Lopatin, M.A.; Holtsberg, F.W.; Ensor, C.M.; Clark, M.A. Clark, Phase I study of uricase formulated with polyethylene glycol (Uricase-PEG 20), Abstract 287.American College of Rheumatology Annual Scientific Meeting; New Orleans, LA, 2002, p. 25-29.
[18]
Pooja, N. JagadeeshBabu, P.E. Studies on the site-specifific PEGylation induced interferences instigated in uricase quantifification using the bradford method. Int. J. Pept. Res. The., 2016, 16, 1-9.
[http://dx.doi.org/10.1007/s10989-016-9518-8]
[19]
Xiaopei, Zh.; Duo, X.; Xin, J. Nanocapsules of therapeutic proteins with enhanced stability and long blood circulation for hyperuricemia management. J. Control. Release, 2017, 2017(255), 54-61.
[http://dx.doi.org/10.1016/j.jconrel.2017.03.019]
[20]
Chen, J.W.T. DNA shuffling of uricase gene leads to a more “human like” chimeric uricase with increased uricolytic activity. Int. J. Biol. Macromol., 2016, 82, 522-529.
[21]
Nelapati, A.K.; Das, B.K.; Ponnan, E.J.B.; Chakraborty, D. In-silico epitope identification and design of Uricase mutein with reduced immunogenicity. Process Biochem., 2020, 92(92), 288-302.
[http://dx.doi.org/10.1016/j.procbio.2020.01.022]
[22]
Sands, E.; Kivitz, A.; DeHaan, W.; Leung, S.S.; Johnston, L.; Kishimoto, T.K. Tolerogenic nanoparticles mitigate the formation of anti-drug antibodies against pegylated uricase in patients with hyperuricemia. Nat. Commun., 2022, 13(1), 272-286.
[http://dx.doi.org/10.1038/s41467-021-27945-7] [PMID: 35022448]
[23]
Schlesinger, N.; Padnick-Silver, L.; LaMoreaux, B. Enchancing the response rate to recombianat uricases in patients with gout. BioDrugs, 2022, 36(2), 95-103.
[http://dx.doi.org/10.1007/s40259-022-00517-x]
[24]
Wu, J.; Chen, G.; Jia, Y.; Ji, C.; Wang, Y.; Zhou, Y.; Leblanc, R.M.; Peng, Z. Carbon dot composites for bioapplications: A review. J. Mater. Chem. B Mater. Biol. Med., 2022, 10(6), 843-869.
[http://dx.doi.org/10.1039/D1TB02446A] [PMID: 35060567]
[25]
Zhang, G.Q.; Li, Y.; Liu, W.P.; Gao, X.F. A fluorimetric and colorimetric dual-signal sensor for hydrogen peroxide and glucose based on the intrinsic peroxidase-like activity of cobalt and nitrogen co-doped carbon dots and inner filter effect. Anal. Methods, 2021, 13(28), 3196-3204.
[http://dx.doi.org/10.1039/D1AY00781E] [PMID: 34184019]
[26]
Rao, C.; Khan, S.; Verma, N.C.; Nandi, C.K. Labelling Proteins with carbon nanodots. ChemBioChem, 2017, 18(24), 2385-2389.
[http://dx.doi.org/10.1002/cbic.201700440] [PMID: 28985453]
[27]
Silva, A.C.A.; Freschi, A.P.P.; Rodrigues, C.M.; Matias, B.F.; Maia, L.P.; Goulart, L.R.; Dantas, N.O. Biological analysis and imaging applications of CdSe/CdSxSe1−x/CdS core–shell magic-sized quantum dot. Nanomedicine, 2016, 12(5), 1421-1430.
[http://dx.doi.org/10.1016/j.nano.2016.01.001]
[28]
Kokorina, A.A.; Bakal, A.A.; Shpuntova, D.V.; Kostritskiy, A.Y.; Beloglazova, N.V.; De Saeger, S.; Sukhorukov, G.B.; Sapelkin, A.V.; Goryacheva, I.Y. Gel electrophoresis separation and origins of light emission in fluorophores prepared from citric acid and ethylenediamine. Sci. Rep., 2019, 9(1), 14665.
[http://dx.doi.org/10.1038/s41598-019-50922-6] [PMID: 31605021]
[29]
Kuznetsova, V.A.; Visheratina, A.K.; Ryan, A.; Martynenko, I.V.; Loudon, A.; Maguire, C.M.; Purcell-Milton, F.; Orlova, A.O.; Baranov, A.V.; Fedorov, A.V.; Prina-Mello, A.; Volkov, Y. Gun’Ko, Y.K. Enantioselective cytotoxicity of ZnS:Mn quantum dots in A549 cells. Chirality, 2017, 29(8), 403-408.
[http://dx.doi.org/10.1002/chir.22713] [PMID: 28608629]
[30]
Yan, M.; Ge, J.; Liu, Z.; Ouyang, P. Encapsulation of single enzyme in nanogel with enhanced biocatalytic activity and stability. J. Am. Chem. Soc., 2006, 128(34), 11008-11009.
[http://dx.doi.org/10.1021/ja064126t] [PMID: 16925402]
[31]
Yunli, Zh.; Mi, Zh.; Dan, H. Uricase alkaline enzymosomes with enhanced stabilities and anti hyperuricemia effects induced by favorable microEnvironmental changes; Scientific Repots, 2016.
[http://dx.doi.org/10.1038/srep20136]
[32]
Zhang, P.; Sun, F.; Tsao, C.; Liu, S.; Jain, P.; Sinclair, A.; Hung, H.C.; Bai, T.; Wu, K.; Jiang, S. Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity. Proc. Natl. Acad. Sci. USA, 2015, 112(39), 12046-12051.
[http://dx.doi.org/10.1073/pnas.1512465112] [PMID: 26371311]
[33]
Kim, S.; Kim, M.; Jung, S.; Kwon, K.; Park, J.; Kim, S.; Kwon, I.; Tae, G. Co-delivery of therapeutic protein and catalase-mimic nanoparticle using a biocompatible nanocarrier for enhanced therapeutic effect. J. Control. Release, 2019, 309, 181-189.
[http://dx.doi.org/10.1016/j.jconrel.2019.07.038] [PMID: 31356840]
[34]
Ming, J.; Zhu, T.; Li, J.; Ye, Z.; Shi, C.; Guo, Z.; Wang, J.; Chen, X.; Zheng, N. A Novel cascade nanoreactor integrating Two-Dimensional Pd-Ru nanozyme, uricase and red blood cell membrane for highly efficient hyperuricemia treatment. Nano-micro. Small, 2021, 17(46), 2103645.
[http://dx.doi.org/10.1002/smll.202103645]
[35]
Zhang, P.; Jain, P.; Tsao, C.; Yuan, Z.; Li, W.; Li, B.; Wu, K.; Hung, H-C.; Lin, X.; Jiang, S. Polypeptides with high zwitterion density for safe and effective therapeutics. Angew. Chem., 2018, 130(26), 7869-7873.
[http://dx.doi.org/10.1002/ange.201802452]
[36]
da Silva Freitas, D.; Spencer, P.J.; Vassão, R.C.; Abrahão-Neto, J. Biochemical and biopharmaceutical properties of PEGylated uricase. Int. J. Pharm., 2010, 387(1-2), 215-222.
[http://dx.doi.org/10.1016/j.ijpharm.2009.11.034] [PMID: 19969053]
[37]
Jun-ichi, T.; Katsumi, H.; Etsuko, K.; Maki, N.; Itary, Y. Studies on antigenicity of the polyethylene glycol (PEG)-modified uricase. Int. J. Immunopharmacol., 1985, 7(5), 725-730.
[http://dx.doi.org/10.1016/0192-0561(85)90158-4] [PMID: 2412977]

Rights & Permissions Print Cite
Article Metrics
23
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy