Multiplexing Nanodrug Ameliorates Liver Fibrosis via ROS Elimination and Inflammation Suppression
Youcui Xu
Department of Orthopaedics, The First Affiliated Hospital of University of Science and Technology of China, Intelligent Nanomedicine Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 P. R. China
Search for more papers by this authorCorresponding Author
Jing Chen
School of Life Sciences, Hefei Normal University, Hefei, 230601 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorWei Jiang
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027 P. R. China
Search for more papers by this authorYangyang Zhao
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027 P. R. China
Search for more papers by this authorChen Yang
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027 P. R. China
Search for more papers by this authorYi Wu
Department of Orthopaedics, The First Affiliated Hospital of University of Science and Technology of China, Intelligent Nanomedicine Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 P. R. China
Search for more papers by this authorQianming Li
Department of Orthopaedics, The First Affiliated Hospital of University of Science and Technology of China, Intelligent Nanomedicine Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 P. R. China
Search for more papers by this authorCorresponding Author
Chen Zhu
Department of Orthopaedics, The First Affiliated Hospital of University of Science and Technology of China, Intelligent Nanomedicine Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorYoucui Xu
Department of Orthopaedics, The First Affiliated Hospital of University of Science and Technology of China, Intelligent Nanomedicine Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 P. R. China
Search for more papers by this authorCorresponding Author
Jing Chen
School of Life Sciences, Hefei Normal University, Hefei, 230601 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorWei Jiang
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027 P. R. China
Search for more papers by this authorYangyang Zhao
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027 P. R. China
Search for more papers by this authorChen Yang
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027 P. R. China
Search for more papers by this authorYi Wu
Department of Orthopaedics, The First Affiliated Hospital of University of Science and Technology of China, Intelligent Nanomedicine Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 P. R. China
Search for more papers by this authorQianming Li
Department of Orthopaedics, The First Affiliated Hospital of University of Science and Technology of China, Intelligent Nanomedicine Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 P. R. China
Search for more papers by this authorCorresponding Author
Chen Zhu
Department of Orthopaedics, The First Affiliated Hospital of University of Science and Technology of China, Intelligent Nanomedicine Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorAbstract
Liver fibrosis is the leading risk factor for hepatocellular carcinoma. Both oxidative stress and inflammation promote the progression of liver fibrosis, but existing therapeutic strategies tend to focus solely on one issue. Additionally, targeting of pathological microstructures is often neglected. Herein, an esterase-responsive carbon quantum dot-dexamethasone (CD-Dex) is developed for liver fibrosis therapy to simultaneously target pathological microstructures, scavenge reactive oxygen species (ROS), and suppress inflammation. Hepatocyte-targeting CD-Dex can efficiently eliminate the intrahepatic ROS, thereby inhibiting the activation of Kupffer cells, preventing further inflammation progression. Moreover, released dexamethasone (Dex) also suppresses inflammatory response by inhibiting the infiltration of inflammatory cells. Antifibrotic experiments demonstrate that CD-Dex significantly alleviates liver injury and collagen deposition, consequently preventing the progression of liver fibrosis. Taken together, these findings suggest that via ROS elimination and inflammation suppression, the newly developed multiplexing nanodrug exhibits great potential in liver fibrosis therapy.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are openly available in figshare at http://doi.org/10.6084/m9.figshare.16680340.
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1T. Kisseleva, D. Brenner, Nat. Rev. Gastroenterol. Hepatol. 2021, 18, 151.
- 2R. Bataller, D. A. Brenner, J. Clin. Invest. 2005, 115, 209.
- 3A. Pellicoro, P. Ramachandran, J. P. Iredale, J. A. Fallowfield, Nat. Rev. Immunol. 2014, 14, 181.
- 4O. Krenkel, F. Tacke, Nat. Rev. Immunol. 2017, 17, 306.
- 5S. L. Friedman, Physiol. Rev. 2008, 88, 125.
- 6S. L. Friedman, J. Hepatol. 2003, 38, 38.
- 7D. Schuppan, Y. O. Kim, J. Clin. Invest. 2013, 123, 1887.
- 8C. Trautwein, S. L. Friedman, D. Schuppan, M. Pinzani, J. Hepatol. 2015, 62, S15.
- 9S. A. Harrison, Z. Goodman, A. Jabbar, R. Vemulapalli, Z. H. Younes, B. Freilich, M. Y. Sheikh, J. M. Schattenberg, Z. Kayali, A. Zivony, A. Sheikh, J. Garcia-Samaniego, S. K. Satapathy, G. Therapondos, E. Mena, D. Schuppan, J. Robinson, J. L. Chan, D. T. Hagerty, A. J. Sanyal, J. Hepatol. 2020, 72, 816.
- 10R. Loomba, E. Lawitz, P. S. Mantry, S. Jayakumar, S. H. Caldwell, H. Arnold, A. M. Diehl, C. S. Djedjos, L. Han, R. P. Myers, G. M. Subramanian, J. G. McHutchison, Z. D. Goodman, N. H. Afdhal, M. R. Charlton, GS-US-384-1497 Investigators, Hepatology 2018, 67, 549.
- 11P. Ferenci, T. M. Scherzer, H. Kerschner, K. Rutter, S. Beinhardt, H. Hofer, M. Schoniger-Hekele, H. Holzmann, P. Steindl-Munda, Gastroenterology 2008, 135, 1561.
- 12T. A. Wynn, T. R. Ramalingam, Nat. Med. 2012, 18, 1028.
- 13L. Anand, A. Choudhury, C. Bihari, B. C. Sharma, M. Kumar, R. Maiwall, S. S. Tan, S. R. Shah, S. Hamid, A. S. Butt, W. Jafri, Y. K. Chawla, S. Taneja, A. Duseja, R. K. Dhiman, M. A. Mahtab, H. Ghazinyan, Z. Duan, Y. Chen, A. Shukla, J. Hu, Z. Abbas, S. Treeprasertsuk, L. A. Lesmana, C. R. Lesmana, J. D. Sollano, G. Carpio, M. K. Sahu, G. Kumar, S. K. Sarin, APASL ACLF (APASL ACLF Research Consortium) Working Party, Hepatology 2019, 70, 587.
- 14C. Corpechot, F. Carrat, A. M. Bonnand, R. E. Poupon, R. Poupon, Hepatology 2000, 32, 1196.
- 15C. O. Zein, L. M. Yerian, P. Gogate, R. Lopez, J. P. Kirwan, A. E. Feldstein, A. J. McCullough, Hepatology 2011, 54, 1610.
- 16S. L. Friedman, V. Ratziu, S. A. Harrison, M. F. Abdelmalek, G. P. Aithal, J. Caballeria, S. Francque, G. Farrell, K. V. Kowdley, A. Craxi, K. Simon, L. Fischer, L. Melchor-Khan, J. Vest, B. L. Wiens, P. Vig, S. Seyedkazemi, Z. Goodman, V. W. Wong, R. Loomba, F. Tacke, A. Sanyal, E. Lefebvre, Hepatology 2018, 67, 1754.
- 17Y. Sato, K. Murase, J. Kato, M. Kobune, T. Sato, Y. Kawano, R. Takimoto, K. Takada, K. Miyanishi, T. Matsunaga, T. Takayama, Y. Niitsu, Nat. Biotechnol. 2008, 26, 431.
- 18J. Wu, J. Huang, S. Kuang, J. Chen, X. Li, B. Chen, J. Wang, D. Cheng, X. Shuai, Adv. Sci. 2019, 6, 1801809.
- 19L. Lin, H. Gong, R. Li, J. Huang, M. Cai, T. Lan, W. Huang, Y. Guo, Z. Zhou, Y. An, Z. Chen, L. Liang, Y. Wang, X. Shuai, K. Zhu, Adv. Sci. 2020, 7, 1903138.
- 20K. Hayashi, T. Maruhashi, W. Sakamoto, T. Yogo, Adv. Funct. Mater. 2018, 28, 1870086.
10.1002/adfm.201870086 Google Scholar
- 21Q. Q. Fan, C. L. Zhang, J. B. Qiao, P. F. Cui, L. Xing, Y. K. Oh, H. L. Jiang, Biomaterials 2020, 230, 119616.
- 22Q. He, J. Zhang, F. Chen, L. Guo, Z. Zhu, J. Shi, Biomaterials 2010, 31, 7785.
- 23J. Luo, P. Zhang, T. Zhao, M. Jia, P. Yin, W. Li, Z. R. Zhang, Y. Fu, T. Gong, ACS Nano 2019, 13, 3910.
- 24H. T. Duong, Z. Dong, L. Su, C. Boyer, J. George, T. P. Davis, J. Wang, Small 2015, 11, 2291.
- 25H. Liang, Z. Li, Z. Ren, Q. Jia, L. Guo, S. Li, H. Zhang, S. Hu, D. Zhu, D. Shen, Z. Yu, K. Cheng, Nano Res. 2020, 13, 2197.
- 26Z. Zhang, C. Wang, Y. Zha, W. Hu, Z. Guo, Y. Zang, J. Chen, J. Zhang, L. Dong, ACS Nano 2015, 9, 2405.
- 27M. Bartneck, K. M. Scheyda, K. T. Warzecha, L. Y. Rizzo, K. Hittatiya, T. Luedde, G. Storm, C. Trautwein, T. Lammers, F. Tacke, Biomaterials 2015, 37, 367.
- 28W. Tang, Z. Zhao, Y. Chong, C. Wu, Q. Liu, J. Yang, R. Zhou, Z. X. Lian, G. Liang, ACS Nano 2018, 12, 9966.
- 29S. Bisht, M. A. Khan, M. Bekhit, H. Bai, T. Cornish, M. Mizuma, M. A. Rudek, M. Zhao, A. Maitra, B. Ray, D. Lahiri, A. Maitra, R. A. Anders, Lab. Invest. 2011, 91, 1383.
- 30D. Oró, T. Yudina, G. Fernández-Varo, E. Casals, V. Reichenbach, G. Casals, B. González de la Presa, S. Sandalinas, S. Carvajal, V. Puntes, W. Jimenez, J. Hepatol. 2016, 64, 691.
- 31X. Bai, G. Su, S. Zhai, Nanomaterials 2020, 10, 1945.
- 32A. Adhikari, N. Polley, S. Darbar, D. Bagchi, S. K. Pal, Future Sci. OA 2016, 2, FSO146.
- 33S. Wilhelm, A. J. Tavares, Q. Dai, S. Ohta, J. Audet, H. F. Dvorak, W. C. W. Chan, Nat. Rev. Mater. 2016, 1, 16014.
- 34C. M. J. Hu, R. H. Fang, K. C. Wang, B. T. Luk, S. Thamphiwatana, D. Dehaini, P. Nguyen, P. Angsantikul, C. H. Wen, A. V. Kroll, C. Carpenter, M. Ramesh, V. Qu, S. H. Patel, J. Zhu, W. Shi, F. M. Hofman, T. C. Chen, W. Gao, K. Zhang, S. Chien, L. Zhang, Nature 2015, 526, 118.
- 35C. Zhang, L. Zhang, W. Wu, F. Gao, R. Q. Li, W. Song, Z. N. Zhuang, C. J. Liu, X. Z. Zhang, Adv. Mater. 2019, 31, 1901179.
- 36W. Geng, N. Jiang, G. Y. Qing, X. Liu, L. Wang, H. J. Busscher, G. Tian, T. Sun, L. Y. Wang, Y. Montelongo, C. Janiak, G. Zhang, X. Y. Yang, B. L. Su, ACS Nano 2019, 13, 14459.
- 37W. Geng, L. Wang, N. Jiang, J. Cao, Y. X. Xiao, H. Wei, A. K. Yetisen, X. Y. Yang, B. L. Su, Nanoscale 2018, 10, 3112.
- 38Y. N. Zhang, W. Poon, A. J. Tavares, I. D. McGilvray, W. C. W. Chan, J. Controlled Release 2016, 240, 332.
- 39H. Wang, C. A. Thorling, X. Liang, K. R. Bridle, J. E. Grice, Y. Zhu, D. H. G. Crawford, Z. P. Xu, X. Liu, M. S. Roberts, J. Mater. Chem. B 2015, 3, 939.
- 40J. Chen, S. Li, Y. Zhang, W. Wang, X. Zhang, Y. Zhao, Y. Wang, H. Bi, Adv. Healthcare Mater. 2017, 6, 1700746.
- 41Y. Koyama, D. A. Brenner, J. Clin. Invest. 2017, 127, 55.
- 42B. S. Ding, Z. Cao, R. Lis, D. J. Nolan, P. Guo, M. Simons, M. E. Penfold, K. Shido, S. Y. Rabbany, S. Rafii, Nature 2014, 505, 97.
- 43X. Wu, X. Wu, Y. Ma, F. Shao, Y. Tan, T. Tan, L. Gu, Y. Zhou, B. Sun, Y. Sun, X. Wu, Q. Xu, Nat. Commun. 2016, 7, 13498.
- 44K. R. Karlmark, R. Weiskirchen, H. W. Zimmermann, N. Gassler, F. Ginhoux, C. Weber, M. Merad, T. Luedde, C. Trautwein, F. Tacke, Hepatology 2009, 50, 261.
- 45K. Iwaisako, M. Haimerl, Y. H. Paik, K. Taura, Y. Kodama, C. Sirlin, E. Yu, R. T. Yu, M. Downes, R. M. Evans, D. A. Brenner, B. Schnabl, Proc. Natl. Acad. Sci. U. S. A. 2012, 109, E1369.
- 46P. J. van den Berg, R. Bansal, K. Daoudi, W. Steenbergen, J. Prakash, Biomed. Opt. Express 2016, 7, 5081.
- 47L. Gailhouste, Y. L.e Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, G. Baffet, J. Hepatol. 2010, 52, 398.
