An ROS-Responsive Antioxidative Macromolecular Prodrug of Caffeate for Uveitis Treatment

Yu-Tong Li; Si-Ting Sheng; Bo Yu; Fan Jia; Kai Wang; Hai-Jie Han; Qiao Jin; You-Xiang Wang; Jian Ji

doi:10.1007/s10118-022-2798-x

Your Location：

Home >

Browse articles >

An ROS-Responsive Antioxidative Macromolecular Prodrug of Caffeate for Uveitis Treatment

RESEARCH ARTICLE | Updated：2022-08-19

- An ROS-Responsive Antioxidative Macromolecular Prodrug of Caffeate for Uveitis Treatment
- Chinese Journal of Polymer Science Vol. 40, Issue 9, Pages: 1101-1109(2022)
- Affiliations：
  
  a.MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China
  b.Eye Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
- Author bio：
  
  kaiwang94@zju.edu.cn (K.W.)
  jijian@zju.edu.cn (J.J.)
- Funds：
- DOI：10.1007/s10118-022-2798-x
  CLC：
Scan for full text
Yu-Tong Li, Si-Ting Sheng, Bo Yu, et al. An ROS-Responsive Antioxidative Macromolecular Prodrug of Caffeate for Uveitis Treatment. [J]. Chinese Journal of Polymer Science 40(9):1101-1109(2022)
DOI：

Yu-Tong Li, Si-Ting Sheng, Bo Yu, et al. An ROS-Responsive Antioxidative Macromolecular Prodrug of Caffeate for Uveitis Treatment. [J]. Chinese Journal of Polymer Science 40(9):1101-1109(2022) DOI： 10.1007/s10118-022-2798-x.

摘要

We developed an ROS-responsive PEGylated polypeptide-based macromolecular ethyl caffeate (EC) prodrug via phenylboronic esters for the alleviation of uveitis. The antioxidative 4-hydroxy benzyl alcohol (HBA) and EC can be released under the stimulation of ROS, which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way.

Abstract

Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species (ROS). Herein, an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate (EC) is designed ,via, phenylboronic esters with improved solubility for the alleviation of uveitis. The antioxidative 4-hydroxybenzyl alcohol (HBA) and EC can be released from the macromolecular EC prodrug under the stimulation of ROS, which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way. The antioxidative and protective effects of the macromolecular EC prodrug ,in vivo, are further verified in a uveitis mouse model. Overall, this work not only provides a handy method to synthesize a phenylboronic ester-bearing EC prodrug which is highly sensitive to pathological ROS, but also depicts a promising future to apply macromolecular antioxidative prodrugs in the treatment of uveitis as well as other ROS-related diseases.

关键词

Keywords

Antioxidative therapyMacromolecular prodrugUveitisEthyl caffeate (EC)Phenylboronic acid esters

references

Lee, R. W.; Nicholson, L. B.; Sen, H. N.; Chan, C. C.; Wei, L.; Nussenblatt, R. B.; Dick, A. D . Autoimmune and autoinflammatory mechanisms in uveitis . Semin. Immunopathol. , 2014 . 36 581 -594 . DOI:10.1007/s00281-014-0433-9http://doi.org/10.1007/s00281-014-0433-9 .

Li, W.; He, B.; Dai, W.; Zhang, Q.; Liu, Y . Evaluations of therapeutic efficacy of intravitreal injected polylactic-glycolic acid microspheres loaded with triamcinolone acetonide on a rabbit model of uveitis . Int. Ophthalmol. , 2014 . 34 465 -476 . DOI:10.1007/s10792-013-9829-0http://doi.org/10.1007/s10792-013-9829-0 .

Mahran, A.; Ismail, S.; Allam, A. A . Development of triamcinolone acetonide-loaded microemulsion as a prospective ophthalmic delivery system for treatment of uveitis: in vitro and in vivo evaluation . Pharmaceutics , 2021 . 13 444 DOI:10.3390/pharmaceutics13040444http://doi.org/10.3390/pharmaceutics13040444 .

Shome, A.; Mugisho, O. O.; Niederer, R. L.; Rupenthal, I. D . Blocking the inflammasome: a novel approach to treat uveitis . Drug Discov. Today , 2021 . 26 2839 -2857 . DOI:10.1016/j.drudis.2021.06.017http://doi.org/10.1016/j.drudis.2021.06.017 .

Garg, V.; Nirmal, J.; Riadi, Y.; Kesharwani, P.; Kohli, K.; Jain, G. K . Amelioration of endotoxin-induced uveitis in rabbit by topical administration of tacrolimus proglycosome nano-vesicles . J. Pharm. Sci. , 2021 . 110 871 -875 . DOI:10.1016/j.xphs.2020.10.060http://doi.org/10.1016/j.xphs.2020.10.060 .

Ung, L.; Pattamatta, U.; Carnt, N.; Wilkinson-Berka, J. L.; Liew, G.; White, A. J. R . Oxidative stress and reactive oxygen species: a review of their role in ocular disease . Clin. Sci. , 2017 . 131 2865 -2883 . DOI:10.1042/CS20171246http://doi.org/10.1042/CS20171246 .

Xu, Q. Y.; Zhang, J.; Qin, T. Y.; Bao, J. Y.; Dong, H. T.; Zhou, X. R.; Hou, S. P.; Mao, L. M . The role of the inflammasomes in the pathogenesis of uveitis . Exp. Eye Res. , 2021 . 208 108618 DOI:10.1016/j.exer.2021.108618http://doi.org/10.1016/j.exer.2021.108618 .

Zhou, R.; Tardivel, A.; Thorens, B.; Choi, I.; Tschopp, J . Thioredoxin-interacting protein links oxidative stress to inflammasome activation . Nat. Immunol. , 2010 . 11 136 -140 . DOI:10.1038/ni.1831http://doi.org/10.1038/ni.1831 .

Ahmad, A.; Ahsan, H . Biomarkers of inflammation and oxidative stress in ophthalmic disorders . J. Immunoassay Immunochem. , 2020 . 41 257 -271 . DOI:10.1080/15321819.2020.1726774http://doi.org/10.1080/15321819.2020.1726774 .

Choulaki, C.; Papadaki, G.; Repa, A.; Kampouraki, E.; Kambas, K.; Ritis, K.; Bertsias, G.; Boumpas, D. T.; Sidiropoulos, P . Enhanced activity of NLRP3 inflammasome in peripheral blood cells of patients with active rheumatoid arthritis . Arthritis Res. Ther. , 2015 . 17 257 DOI:10.1186/s13075-015-0775-2http://doi.org/10.1186/s13075-015-0775-2 .

Ou, A. T.; Zhang, J. X.; Fang, Y. F.; Wang, R.; Tang, X. P.; Zhao, P. F.; Zhao, Y. G.; Zhang, M.; Huang, Y. Z . Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases . Acta Pharmacol. Sin. , 2021 . 42 1913 -1920 . DOI:10.1038/s41401-021-00770-whttp://doi.org/10.1038/s41401-021-00770-w .

Mishra, S. R.; Mahapatra, K. K.; Behera, B. P.; Patra, S.; Bhol, C. S.; Panigrahi, D. P.; Praharaj, P. P.; Singh, A.; Patil, S.; Dhiman, R.; Bhutia, S. K . Mitochondrial dysfunction as a driver of NLRP3 inflammasome activation and its modulation through mitophagy for potential therapeutics . Int. J. Biochem. Cell Biol. , 2021 . 136 106013 DOI:10.1016/j.biocel.2021.106013http://doi.org/10.1016/j.biocel.2021.106013 .

van der Vliet, A.; Janssen-Heininger, Y. M . Hydrogen peroxide as a damage signal in tissue injury and inflammation: murderer, mediator, or messenger . J. Cell. Biochem. , 2014 . 115 427 -435 . DOI:10.1002/jcb.24683http://doi.org/10.1002/jcb.24683 .

Halliwell, B . Biochemistry of oxidative stress . Biochem. Soc. Trans. , 2007 . 35 1147 -1150 . DOI:10.1042/BST0351147http://doi.org/10.1042/BST0351147 .

Yadav, U. C. S.; Kalariya, N. M.; Ramana, K. V . Emerging role of antioxidants in the protection of uveitis complications . Curr. Med. Chem. , 2011 . 18 931 -942 . DOI:10.2174/092986711794927694http://doi.org/10.2174/092986711794927694 .

Li, Z.; Li, H.; Zhang, J.; Liu, X.; Gu, Z.; Li, Y . Ultrasmall nanoparticle ROS scavengers based on polyhedral oligomeric silsesquioxanes . Chinese J. Polym. Sci. , 2020 . 38 1149 -1156 . DOI:10.1007/s10118-020-2486-7http://doi.org/10.1007/s10118-020-2486-7 .

Granata, G.; Paterniti, I.; Geraci, C.; Cunsolo, F.; Esposito, E.; Cordaro, M.; Blanco, A. R.; Cuzzocrea, S.; Consoli, G. M. L . Potential eye drop based on a calix[4]arene nanoassembly for curcumin delivery: enhanced drug solubility, stability, and anti-inflammatory effect . Mol. Pharm. , 2017 . 14 1610 -1622 . DOI:10.1021/acs.molpharmaceut.6b01066http://doi.org/10.1021/acs.molpharmaceut.6b01066 .

Deng, J.; Lin, D. Q.; Ding, X. Y.; Wang, Y.; Hu, Y. H.; Shi, H.; Chen, L.; Chu, B. Y.; Lei, L.; Wen, C. M.; Wang, J. Q.; Qian, Z. Y.; Li, X. Y . Multifunctional supramolecular filament hydrogel boosts anti-inflammatory efficacy in vitro and in vivo . Adv. Funct. Mater. , 2022 . 32 2109173 DOI:10.1002/adfm.202109173http://doi.org/10.1002/adfm.202109173 .

Masuda, T.; Yamada, K.; Akiyama, J.; Someya, T.; Odaka, Y.; Takeda, Y.; Tori, M.; Nakashima, K.; Maekawa, T.; Sone, Y . Antioxidation mechanism studies of caffeic acid: identification of antioxidation products of methyl caffeate from lipid oxidation . J. Agric. Food Chem. , 2008 . 56 5947 -5952 . DOI:10.1021/jf800781bhttp://doi.org/10.1021/jf800781b .

Chiang, Y. M.; Lo, C. P.; Chen, Y. P.; Wang, S. Y.; Yang, N. S.; Kuo, Y. H.; Shyur, L. F . Ethyl caffeate suppresses NF-kappaB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE2 in vitro or in mouse skin . Br. J. Pharmacol. , 2005 . 146 352 -363 . DOI:10.1038/sj.bjp.0706343http://doi.org/10.1038/sj.bjp.0706343 .

Mao, Y. W.; Tseng, H. W.; Liang, W. L.; Chen, I. S.; Chen, S. T.; Lee, M. H . Anti-inflammatory and free radial scavenging activities of the constituents isolated from Machilus zuihoensis . Molecules , 2011 . 16 9451 -9466 . DOI:10.3390/molecules16119451http://doi.org/10.3390/molecules16119451 .

Kularatne, R. N.; Bulumulla, C.; Catchpole, T.; Takacs, A.; Christie, A.; Stefan, M. C.; Csaky, K. G . Protection of human retinal pigment epithelial cells from oxidative damage using cysteine prodrugs . Free Radic. Biol. Med. , 2020 . 152 386 -394 . DOI:10.1016/j.freeradbiomed.2020.03.024http://doi.org/10.1016/j.freeradbiomed.2020.03.024 .

Muangnoi, C.; Phumsuay, R.; Jongjitphisut, N.; Waikasikorn, P.; Sangsawat, M.; Rashatasakhon, P.; Paraoan, L.; Rojsitthisak, P . Protective effects of a lutein ester prodrug, lutein diglutaric acid, against H2O2-induced oxidative stress in human retinal pigment epithelial cells . Int. J. Mol. Sci. , 2021 . 22 4722 DOI:10.3390/ijms22094722http://doi.org/10.3390/ijms22094722 .

Zhang, C.; Lu, H. . Helical nonfouling polypeptides for biomedical applications . Chinese J. Polym. Sci. , 2022 . 40 433 -446 . DOI:10.1007/s10118-022-2688-2http://doi.org/10.1007/s10118-022-2688-2 .

Song, Z.; Han, Z.; Lv, S.; Chen, C.; Chen, L.; Yin, L.; Cheng, J . Synthetic polypeptides: from polymer design to supramolecular assembly and biomedical application . Chem. Soc. Rev. , 2017 . 46 6570 -6599 . DOI:10.1039/C7CS00460Ehttp://doi.org/10.1039/C7CS00460E .

Liu, Y.; Li, D.; Ding, J.; Chen, X . Controlled synthesis of polypeptides . Chin. Chem. Lett. , 2020 . 31 3001 -3014 . DOI:10.1016/j.cclet.2020.04.029http://doi.org/10.1016/j.cclet.2020.04.029 .

Ren, J.; Shu, X.; Wang, Y.; Wang, D.; Wu, G.; Zhang, X.; Jin, Q.; Liu, J.; Wu, Z.; Xu, Z.; Li, C. Z.; Li, H . Key progresses of MOE key laboratory of macromolecular synthesis and functionalization in 2020 . Chin. Chem. Lett. , 2022 . 33 1650 -1658 . DOI:10.1016/j.cclet.2021.10.052http://doi.org/10.1016/j.cclet.2021.10.052 .

Xiong, R.; Xu, R . X.; Huang, C.; De Smedt, S.; Braeckmans, K. Stimuli-responsive nanobubbles for biomedical applications . Chem. Soc. Rev. , 2021 . 50 5746 -5776 . DOI:10.1039/C9CS00839Jhttp://doi.org/10.1039/C9CS00839J .

Han, H.; Hou, Y.; Chen, X.; Zhang, P.; Kang, M.; Jin, Q.; Ji, J.; Gao, M . Metformin-induced stromal depletion to enhance the penetration of gemcitabine-loaded magnetic nanoparticles for pancreatic cancer targeted therapy . J. Am. Chem. Soc. , 2020 . 142 4944 -4954 . DOI:10.1021/jacs.0c00650http://doi.org/10.1021/jacs.0c00650 .

Gao, Y.; Wang, J.; Chai, M.; Li, X.; Deng, Y.; Jin, Q.; Ji, J . Size and charge adaptive clustered nanoparticles targeting the biofilm microenvironment for chronic lung infection management . ACS Nano , 2020 . 14 5686 -5699 . DOI:10.1021/acsnano.0c00269http://doi.org/10.1021/acsnano.0c00269 .

Deng, Y.; Wang, Y.; Jia, F.; Liu, W.; Zhou, D.; Jin, Q.; Ji, J . Tailoring supramolecular prodrug nanoassemblies for reactive nitrogen species-potentiated chemotherapy of liver cancer . ACS Nano , 2021 . 15 8663 -8675 . DOI:10.1021/acsnano.1c00698http://doi.org/10.1021/acsnano.1c00698 .

Tao, W.; He, Z . ROS-responsive drug delivery systems for biomedical applications . Asian J. Pharm. Sci. , 2018 . 13 101 -112 . DOI:10.1016/j.ajps.2017.11.002http://doi.org/10.1016/j.ajps.2017.11.002 .

Xu, Q.; He, C.; Xiao, C.; Chen, X . Reactive oxygen species (ROS) responsive polymers for biomedical applications . Macromol. Biosci. , 2016 . 16 635 -646 . DOI:10.1002/mabi.201500440http://doi.org/10.1002/mabi.201500440 .

Broaders, K. E.; Grandhe, S.; Frechet, J. M . A biocompatible oxidation-triggered carrier polymer with potential in therapeutics . J. Am. Chem. Soc. , 2011 . 133 756 -758 . DOI:10.1021/ja110468vhttp://doi.org/10.1021/ja110468v .

Liu, D.; Cornel, E. J.; Du, J . Renoprotective angiographic polymersomes . Adv. Funct. Mater. , 2020 . 31 2007330 DOI:10.1002/adfm.202007330http://doi.org/10.1002/adfm.202007330 .

Tian, Z . Y.; Zhang, Z.; Wang, S.; Lu, H. A moisture-tolerant route to unprotected α/β-amino acid N-carboxyanhydrides and facile synthesis of hyperbranched polypeptides . Nat. Commun. , 2021 . 12 5810 DOI:10.1038/s41467-021-25689-yhttp://doi.org/10.1038/s41467-021-25689-y .

Qiu, Y.; Shil, P . K.; Zhu, P.; Yang, H.; Verma, A.; Lei, B.; Li, Q. Angiotensin-converting enzyme 2 (ACE2) activator diminazene aceturate ameliorates endotoxin-induced uveitis in mice . Invest. Ophthalmol. Vis. Sci. , 2014 . 55 3809 -3818 . DOI:10.1167/iovs.14-13883http://doi.org/10.1167/iovs.14-13883 .

Yang, Z.; Min, Z.; Yu, B . Reactive oxygen species and immune regulation . Int. Rev. Immunol. , 2020 . 39 292 -298 . DOI:10.1080/08830185.2020.1768251http://doi.org/10.1080/08830185.2020.1768251 .

Weinstein, J. E.; Pepple, K. L . Cytokines in uveitis . Curr. Opin. Ophthalmol. , 2018 . 29 267 -274 . DOI:10.1097/ICU.0000000000000466http://doi.org/10.1097/ICU.0000000000000466 .

Yuan, H.; Xu, Y.; Luo, Y.; Wang, N. X.; Xiao, J. H . Role of Nrf2 in cell senescence regulation . Mol. Cell. Biochem. , 2021 . 476 247 -259 . DOI:10.1007/s11010-020-03901-9http://doi.org/10.1007/s11010-020-03901-9 .

Bao, M.; Liang, M.; Sun, X.; Mohyuddin, S. G.; Chen, S.; Wen, J.; Yong, Y.; Ma, X.; Yu, Z.; Ju, X.; Liu, X. . Baicalin alleviates LPS-induced oxidative stress via NF-kappaB and Nrf2-HO1 signaling pathways in IPEC-J2 cells . Front. Vet. Sci. , 2021 . 8 808233 DOI:10.3389/fvets.2021.808233http://doi.org/10.3389/fvets.2021.808233 .

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

No data

Related Author

No data

Related Institution

No data

⁰