Antioxidant and C5a-blocking strategy for hepatic ischemia–reperfusion injury repair
Abstract Background Nonspecific liver uptake of nanomaterials after intravenous injection has hindered nanomedicine for clinical translation. However, nanomaterials’ propensity for liver distribution might enable their use in hepatic ischemia–reperfusion injury (IRI) repair. During hepatic IRI, reac...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-04-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-021-00858-9 |
| _version_ | 1811186630196723712 |
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| author | Xiaobing Zhang Jiajia Hu Kaelyn V. Becker Jonathan W. Engle Dalong Ni Weibo Cai Dong Wu Shuping Qu |
| author_facet | Xiaobing Zhang Jiajia Hu Kaelyn V. Becker Jonathan W. Engle Dalong Ni Weibo Cai Dong Wu Shuping Qu |
| author_sort | Xiaobing Zhang |
| collection | DOAJ |
| description | Abstract Background Nonspecific liver uptake of nanomaterials after intravenous injection has hindered nanomedicine for clinical translation. However, nanomaterials’ propensity for liver distribution might enable their use in hepatic ischemia–reperfusion injury (IRI) repair. During hepatic IRI, reactive oxygen species (ROS) are generated and the fifth component of complement (C5a) is activated. In addition, C5a is confirmed to exacerbate the vicious cycle of oxidative stress and inflammatory damage. For these reasons, we have investigated the development of nanomaterials with liver uptake to scavenge ROS and block C5a for hepatic IRI repair. Results To achieve this goal, a traditional nanoantioxidant of nanoceria was surface conjugated with the anti-C5a aptamers (Ceria@Apt) to scavenge the ROS and reduce C5a-mediated inflammation. High uptake of Ceria@Apt in the liver was confirmed by preclinical positron emission tomography (PET) imaging. The clinical symptoms of hepatic IRI were effectively alleviated by Ceria@Apt with ROS scavenging and C5a blocking in mice model. The released pro-inflammatory cytokines were significantly reduced, and subsequent inflammatory reaction involved in the liver was inhibited. Conclusions The synthesized Ceria@Apt has great potential of medical application in hepatic IRI repair, which could also be applied for other ischemic-related diseases. Graphic abstract |
| first_indexed | 2024-04-11T13:49:25Z |
| format | Article |
| id | doaj.art-97e2fe4cdbf04833843de403a31df5f2 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T13:49:25Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-97e2fe4cdbf04833843de403a31df5f22022-12-22T04:20:48ZengBMCJournal of Nanobiotechnology1477-31552021-04-0119111010.1186/s12951-021-00858-9Antioxidant and C5a-blocking strategy for hepatic ischemia–reperfusion injury repairXiaobing Zhang0Jiajia Hu1Kaelyn V. Becker2Jonathan W. Engle3Dalong Ni4Weibo CaiDong Wu5Shuping Qu6Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical UniversityDepartment of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartments of Radiology and Medical Physics, University of Wisconsin–MadisonDepartments of Radiology and Medical Physics, University of Wisconsin–MadisonDepartments of Radiology and Medical Physics, University of Wisconsin–MadisonDepartment of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical UniversityDepartment of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical UniversityAbstract Background Nonspecific liver uptake of nanomaterials after intravenous injection has hindered nanomedicine for clinical translation. However, nanomaterials’ propensity for liver distribution might enable their use in hepatic ischemia–reperfusion injury (IRI) repair. During hepatic IRI, reactive oxygen species (ROS) are generated and the fifth component of complement (C5a) is activated. In addition, C5a is confirmed to exacerbate the vicious cycle of oxidative stress and inflammatory damage. For these reasons, we have investigated the development of nanomaterials with liver uptake to scavenge ROS and block C5a for hepatic IRI repair. Results To achieve this goal, a traditional nanoantioxidant of nanoceria was surface conjugated with the anti-C5a aptamers (Ceria@Apt) to scavenge the ROS and reduce C5a-mediated inflammation. High uptake of Ceria@Apt in the liver was confirmed by preclinical positron emission tomography (PET) imaging. The clinical symptoms of hepatic IRI were effectively alleviated by Ceria@Apt with ROS scavenging and C5a blocking in mice model. The released pro-inflammatory cytokines were significantly reduced, and subsequent inflammatory reaction involved in the liver was inhibited. Conclusions The synthesized Ceria@Apt has great potential of medical application in hepatic IRI repair, which could also be applied for other ischemic-related diseases. Graphic abstracthttps://doi.org/10.1186/s12951-021-00858-9Hepatic ischemia–reperfusion injuryNanoantioxidantsC5aNanoceriaAptamer |
| spellingShingle | Xiaobing Zhang Jiajia Hu Kaelyn V. Becker Jonathan W. Engle Dalong Ni Weibo Cai Dong Wu Shuping Qu Antioxidant and C5a-blocking strategy for hepatic ischemia–reperfusion injury repair Journal of Nanobiotechnology Hepatic ischemia–reperfusion injury Nanoantioxidants C5a Nanoceria Aptamer |
| title | Antioxidant and C5a-blocking strategy for hepatic ischemia–reperfusion injury repair |
| title_full | Antioxidant and C5a-blocking strategy for hepatic ischemia–reperfusion injury repair |
| title_fullStr | Antioxidant and C5a-blocking strategy for hepatic ischemia–reperfusion injury repair |
| title_full_unstemmed | Antioxidant and C5a-blocking strategy for hepatic ischemia–reperfusion injury repair |
| title_short | Antioxidant and C5a-blocking strategy for hepatic ischemia–reperfusion injury repair |
| title_sort | antioxidant and c5a blocking strategy for hepatic ischemia reperfusion injury repair |
| topic | Hepatic ischemia–reperfusion injury Nanoantioxidants C5a Nanoceria Aptamer |
| url | https://doi.org/10.1186/s12951-021-00858-9 |
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