Co-delivery of miR-29b and germacrone based on cyclic RGD-modified nanoparticles for liver fibrosis therapy
Abstract Hepatic stellate cells (HSCs) were activated and secreted excessive amounts of extracellular matrix (ECM) proteins during pathogenetic progress of liver fibrosis. Germacrone (GMO) and miR-29b can play an important role in inhibiting growth of HSCs and production of type I collagen. GMO and...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12951-020-00645-y |
| _version_ | 1798006063688056832 |
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| author | De Ji Qiaohan Wang Qi Zhao Huangjin Tong Mengting Yu Meng Wang Tulin Lu Chengxi Jiang |
| author_facet | De Ji Qiaohan Wang Qi Zhao Huangjin Tong Mengting Yu Meng Wang Tulin Lu Chengxi Jiang |
| author_sort | De Ji |
| collection | DOAJ |
| description | Abstract Hepatic stellate cells (HSCs) were activated and secreted excessive amounts of extracellular matrix (ECM) proteins during pathogenetic progress of liver fibrosis. Germacrone (GMO) and miR-29b can play an important role in inhibiting growth of HSCs and production of type I collagen. GMO and miR-29b were co-encapsulated into nanoparticles (NPs) based on poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA). Then, NPs were modified with cyclic RGD peptides (cRGDfK). cRGDfK is an effective ligand to bind integrin αvβ3 and increase the targeting ability for fibrotic liver. GMO- and miR-29b-loaded NPs exhibited great cytotoxicity to activated HSCs and significantly inhibited production of type I collagen. Liver fibrosis model of mice was induced by administration of carbon tetrachloride. Great targeting ability was achieved in liver fibrotic mice treated with cRGD-modified NPs. Significant ant-fibrotic effects have been presented based on hematoxylin and eosin (H&E), Masson and Sirius Red staining results of liver tissues collected from mice treated with drug-loaded NPs. All these results indicate GMO- and miR-29b-loaded cRGD-modified NPs have the potential for clinical use to treat liver fibrosis. |
| first_indexed | 2024-04-11T12:48:59Z |
| format | Article |
| id | doaj.art-dae89dc8c2034285b0e7bedf3cb86bf5 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T12:48:59Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-dae89dc8c2034285b0e7bedf3cb86bf52022-12-22T04:23:15ZengBMCJournal of Nanobiotechnology1477-31552020-06-0118111110.1186/s12951-020-00645-yCo-delivery of miR-29b and germacrone based on cyclic RGD-modified nanoparticles for liver fibrosis therapyDe Ji0Qiaohan Wang1Qi Zhao2Huangjin Tong3Mengting Yu4Meng Wang5Tulin Lu6Chengxi Jiang7School of Pharmacy, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineMolecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical UniversityAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineMolecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical UniversityAbstract Hepatic stellate cells (HSCs) were activated and secreted excessive amounts of extracellular matrix (ECM) proteins during pathogenetic progress of liver fibrosis. Germacrone (GMO) and miR-29b can play an important role in inhibiting growth of HSCs and production of type I collagen. GMO and miR-29b were co-encapsulated into nanoparticles (NPs) based on poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA). Then, NPs were modified with cyclic RGD peptides (cRGDfK). cRGDfK is an effective ligand to bind integrin αvβ3 and increase the targeting ability for fibrotic liver. GMO- and miR-29b-loaded NPs exhibited great cytotoxicity to activated HSCs and significantly inhibited production of type I collagen. Liver fibrosis model of mice was induced by administration of carbon tetrachloride. Great targeting ability was achieved in liver fibrotic mice treated with cRGD-modified NPs. Significant ant-fibrotic effects have been presented based on hematoxylin and eosin (H&E), Masson and Sirius Red staining results of liver tissues collected from mice treated with drug-loaded NPs. All these results indicate GMO- and miR-29b-loaded cRGD-modified NPs have the potential for clinical use to treat liver fibrosis.http://link.springer.com/article/10.1186/s12951-020-00645-yHepatic stellate cellsGermacronemiR-29bcRGDfKLiver fibrosis therapy |
| spellingShingle | De Ji Qiaohan Wang Qi Zhao Huangjin Tong Mengting Yu Meng Wang Tulin Lu Chengxi Jiang Co-delivery of miR-29b and germacrone based on cyclic RGD-modified nanoparticles for liver fibrosis therapy Journal of Nanobiotechnology Hepatic stellate cells Germacrone miR-29b cRGDfK Liver fibrosis therapy |
| title | Co-delivery of miR-29b and germacrone based on cyclic RGD-modified nanoparticles for liver fibrosis therapy |
| title_full | Co-delivery of miR-29b and germacrone based on cyclic RGD-modified nanoparticles for liver fibrosis therapy |
| title_fullStr | Co-delivery of miR-29b and germacrone based on cyclic RGD-modified nanoparticles for liver fibrosis therapy |
| title_full_unstemmed | Co-delivery of miR-29b and germacrone based on cyclic RGD-modified nanoparticles for liver fibrosis therapy |
| title_short | Co-delivery of miR-29b and germacrone based on cyclic RGD-modified nanoparticles for liver fibrosis therapy |
| title_sort | co delivery of mir 29b and germacrone based on cyclic rgd modified nanoparticles for liver fibrosis therapy |
| topic | Hepatic stellate cells Germacrone miR-29b cRGDfK Liver fibrosis therapy |
| url | http://link.springer.com/article/10.1186/s12951-020-00645-y |
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