Control release of mitochondria-targeted antioxidant by injectable self-assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injury
Persistent mitochondrial injury occurs after acute kidney injury (AKI) and mitochondria-targeted antioxidant Mito-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) (MT) has shown benefits for AKI, but its efficiency is limited by short half-life and side effect in vivo. Self-assembling peptide (SAP) hydr...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-01-01
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| Series: | Drug Delivery |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/10717544.2018.1440445 |
| _version_ | 1819023267954950144 |
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| author | Meng Zhao Yijie Zhou Shuyun Liu Lan Li Younan Chen Jingqiu Cheng Yanrong Lu Jingping Liu |
| author_facet | Meng Zhao Yijie Zhou Shuyun Liu Lan Li Younan Chen Jingqiu Cheng Yanrong Lu Jingping Liu |
| author_sort | Meng Zhao |
| collection | DOAJ |
| description | Persistent mitochondrial injury occurs after acute kidney injury (AKI) and mitochondria-targeted antioxidant Mito-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) (MT) has shown benefits for AKI, but its efficiency is limited by short half-life and side effect in vivo. Self-assembling peptide (SAP) hydrogel is a robust platform for drug delivery. This study aims to develop an SAP-based carrier to slow release MT for enhancing its long-term therapeutic potency on AKI. The KLD with aspartic acid (KLDD) was designed. The microstructure and in vitro release of MT was assayed. The protective role of MT-loaded SAP (SAP-MT) hydrogel on renal mitochondrial injury, tubular apoptosis, and inflammation was evaluated in mice at five days after ischemia-reperfusion injury (IRI). Our results showed that KLDD could self-assemble into cross-linked nanofiber hydrogel and it had lower release rate than free MT and KLD hydrogel. Compared to IRI and free MT mice, SAP-MT mice exerted reduced renal mitochondria-produced ROS (mtROS) and improved mitochondrial biogenesis and architecture. Consequently, SAP-MT mice showed less renal tubular cell apoptosis, kidney injury marker kidney injury molecule-1 (Kim-1) expression, lower level of pro-inflammatory factors expression, and macrophages infiltration than those of IRI and free MT mice. This study suggested that SAP-MT ameliorated IRI due to its extended mitochondrial protection role than free MT and thus improved the long-term outcomes of AKI. |
| first_indexed | 2024-12-21T04:36:11Z |
| format | Article |
| id | doaj.art-54559cc37dc242f29155ead891af3130 |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-12-21T04:36:11Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-54559cc37dc242f29155ead891af31302022-12-21T19:15:51ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642018-01-0125154655410.1080/10717544.2018.14404451440445Control release of mitochondria-targeted antioxidant by injectable self-assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injuryMeng Zhao0Yijie Zhou1Shuyun Liu2Lan Li3Younan Chen4Jingqiu Cheng5Yanrong Lu6Jingping Liu7West China Hospital, Sichuan UniversityWest China Hospital, Sichuan UniversityWest China Hospital, Sichuan UniversityWest China Hospital, Sichuan UniversityWest China Hospital, Sichuan UniversityWest China Hospital, Sichuan UniversityWest China Hospital, Sichuan UniversityWest China Hospital, Sichuan UniversityPersistent mitochondrial injury occurs after acute kidney injury (AKI) and mitochondria-targeted antioxidant Mito-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) (MT) has shown benefits for AKI, but its efficiency is limited by short half-life and side effect in vivo. Self-assembling peptide (SAP) hydrogel is a robust platform for drug delivery. This study aims to develop an SAP-based carrier to slow release MT for enhancing its long-term therapeutic potency on AKI. The KLD with aspartic acid (KLDD) was designed. The microstructure and in vitro release of MT was assayed. The protective role of MT-loaded SAP (SAP-MT) hydrogel on renal mitochondrial injury, tubular apoptosis, and inflammation was evaluated in mice at five days after ischemia-reperfusion injury (IRI). Our results showed that KLDD could self-assemble into cross-linked nanofiber hydrogel and it had lower release rate than free MT and KLD hydrogel. Compared to IRI and free MT mice, SAP-MT mice exerted reduced renal mitochondria-produced ROS (mtROS) and improved mitochondrial biogenesis and architecture. Consequently, SAP-MT mice showed less renal tubular cell apoptosis, kidney injury marker kidney injury molecule-1 (Kim-1) expression, lower level of pro-inflammatory factors expression, and macrophages infiltration than those of IRI and free MT mice. This study suggested that SAP-MT ameliorated IRI due to its extended mitochondrial protection role than free MT and thus improved the long-term outcomes of AKI.http://dx.doi.org/10.1080/10717544.2018.1440445acute kidney injurymitochondriamito-tempoself-assembling peptidecontrol release |
| spellingShingle | Meng Zhao Yijie Zhou Shuyun Liu Lan Li Younan Chen Jingqiu Cheng Yanrong Lu Jingping Liu Control release of mitochondria-targeted antioxidant by injectable self-assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injury Drug Delivery acute kidney injury mitochondria mito-tempo self-assembling peptide control release |
| title | Control release of mitochondria-targeted antioxidant by injectable self-assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injury |
| title_full | Control release of mitochondria-targeted antioxidant by injectable self-assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injury |
| title_fullStr | Control release of mitochondria-targeted antioxidant by injectable self-assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injury |
| title_full_unstemmed | Control release of mitochondria-targeted antioxidant by injectable self-assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injury |
| title_short | Control release of mitochondria-targeted antioxidant by injectable self-assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injury |
| title_sort | control release of mitochondria targeted antioxidant by injectable self assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injury |
| topic | acute kidney injury mitochondria mito-tempo self-assembling peptide control release |
| url | http://dx.doi.org/10.1080/10717544.2018.1440445 |
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