Hepatocyte-targeted hyaluronic acid-polyethyleneimine conjugates for acute liver injury therapy by ROS elimination and inflammation modulation
Acute liver injury (ALI) is one of the most important causes of liver failure, and there are no FDA-approved drugs that could therapy late-stage ALI. It has been shown in this study that HA-PEI, a molecule formed by covalently combining HA and PEI, can effectively treat advanced ALI. Through the CD4...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Materials & Design |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0264127523006275 |
| _version_ | 1797671478272983040 |
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| author | Mingqiao Li Hedan Xu Nan Zhao Liangjun Zhang Haihan Xia Xiaoxun Zhang Qiao Li Min Liao Qiong Pan Zeng Yi Jin Chai |
| author_facet | Mingqiao Li Hedan Xu Nan Zhao Liangjun Zhang Haihan Xia Xiaoxun Zhang Qiao Li Min Liao Qiong Pan Zeng Yi Jin Chai |
| author_sort | Mingqiao Li |
| collection | DOAJ |
| description | Acute liver injury (ALI) is one of the most important causes of liver failure, and there are no FDA-approved drugs that could therapy late-stage ALI. It has been shown in this study that HA-PEI, a molecule formed by covalently combining HA and PEI, can effectively treat advanced ALI. Through the CD44 receptor, HA-PEI could target the liver actively, with the highest liver-targeting effect confirmed at 1000 K. The underlying mechanism of protection of HA-PEI is by increasing oxygen content, reducing ROS, and maintaining mitochondrial membrane potential. HA-PEI also inhibits the secretion of inflammatory factors and blocks the migration of immune cells to the liver, protecting the hepatocytes not suffer from secondary damage. More importantly, for late-stage ALI, NAC, as the only FDA-approved drug, is completely ineffective, whereas HA-PEI has an excellent therapeutic effect. This work provides a new safe therapeutic agent for ALI, which has a bright application prospect. |
| first_indexed | 2024-03-11T21:16:07Z |
| format | Article |
| id | doaj.art-951da61ecb3248e89ad2bf786b630bd0 |
| institution | Directory Open Access Journal |
| issn | 0264-1275 |
| language | English |
| last_indexed | 2024-03-11T21:16:07Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj.art-951da61ecb3248e89ad2bf786b630bd02023-09-29T04:43:23ZengElsevierMaterials & Design0264-12752023-09-01233112212Hepatocyte-targeted hyaluronic acid-polyethyleneimine conjugates for acute liver injury therapy by ROS elimination and inflammation modulationMingqiao Li0Hedan Xu1Nan Zhao2Liangjun Zhang3Haihan Xia4Xiaoxun Zhang5Qiao Li6Min Liao7Qiong Pan8Zeng Yi9Jin Chai10Department of Gastroenterology, 2 Institute of Digestive Diseases of PLA, 3 Cholestatic Liver Diseases Center, and 4 Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Pediatric, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Gastroenterology, 2 Institute of Digestive Diseases of PLA, 3 Cholestatic Liver Diseases Center, and 4 Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Gastroenterology, 2 Institute of Digestive Diseases of PLA, 3 Cholestatic Liver Diseases Center, and 4 Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Gastroenterology, 2 Institute of Digestive Diseases of PLA, 3 Cholestatic Liver Diseases Center, and 4 Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Gastroenterology, 2 Institute of Digestive Diseases of PLA, 3 Cholestatic Liver Diseases Center, and 4 Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Gastroenterology, 2 Institute of Digestive Diseases of PLA, 3 Cholestatic Liver Diseases Center, and 4 Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Gastroenterology, 2 Institute of Digestive Diseases of PLA, 3 Cholestatic Liver Diseases Center, and 4 Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Gastroenterology, 2 Institute of Digestive Diseases of PLA, 3 Cholestatic Liver Diseases Center, and 4 Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, ChinaCollege of Biomedical Engineering, Sichuan University, Chengdu 610064, China; Corresponding authors.Department of Gastroenterology, 2 Institute of Digestive Diseases of PLA, 3 Cholestatic Liver Diseases Center, and 4 Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, China; Corresponding authors.Acute liver injury (ALI) is one of the most important causes of liver failure, and there are no FDA-approved drugs that could therapy late-stage ALI. It has been shown in this study that HA-PEI, a molecule formed by covalently combining HA and PEI, can effectively treat advanced ALI. Through the CD44 receptor, HA-PEI could target the liver actively, with the highest liver-targeting effect confirmed at 1000 K. The underlying mechanism of protection of HA-PEI is by increasing oxygen content, reducing ROS, and maintaining mitochondrial membrane potential. HA-PEI also inhibits the secretion of inflammatory factors and blocks the migration of immune cells to the liver, protecting the hepatocytes not suffer from secondary damage. More importantly, for late-stage ALI, NAC, as the only FDA-approved drug, is completely ineffective, whereas HA-PEI has an excellent therapeutic effect. This work provides a new safe therapeutic agent for ALI, which has a bright application prospect.http://www.sciencedirect.com/science/article/pii/S0264127523006275Hepatocyte-targettingLiver injuryCationic hyaluronicROS eliminationInflammation modulation |
| spellingShingle | Mingqiao Li Hedan Xu Nan Zhao Liangjun Zhang Haihan Xia Xiaoxun Zhang Qiao Li Min Liao Qiong Pan Zeng Yi Jin Chai Hepatocyte-targeted hyaluronic acid-polyethyleneimine conjugates for acute liver injury therapy by ROS elimination and inflammation modulation Materials & Design Hepatocyte-targetting Liver injury Cationic hyaluronic ROS elimination Inflammation modulation |
| title | Hepatocyte-targeted hyaluronic acid-polyethyleneimine conjugates for acute liver injury therapy by ROS elimination and inflammation modulation |
| title_full | Hepatocyte-targeted hyaluronic acid-polyethyleneimine conjugates for acute liver injury therapy by ROS elimination and inflammation modulation |
| title_fullStr | Hepatocyte-targeted hyaluronic acid-polyethyleneimine conjugates for acute liver injury therapy by ROS elimination and inflammation modulation |
| title_full_unstemmed | Hepatocyte-targeted hyaluronic acid-polyethyleneimine conjugates for acute liver injury therapy by ROS elimination and inflammation modulation |
| title_short | Hepatocyte-targeted hyaluronic acid-polyethyleneimine conjugates for acute liver injury therapy by ROS elimination and inflammation modulation |
| title_sort | hepatocyte targeted hyaluronic acid polyethyleneimine conjugates for acute liver injury therapy by ros elimination and inflammation modulation |
| topic | Hepatocyte-targetting Liver injury Cationic hyaluronic ROS elimination Inflammation modulation |
| url | http://www.sciencedirect.com/science/article/pii/S0264127523006275 |
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