Targeting glutamine synthetase with AS1411-modified exosome-liposome hybrid nanoparticles for inhibition of choroidal neovascularization
Abstract Choroidal neovascularization (CNV) is a leading cause of visual impairment in wet age-related macular degeneration (wAMD). Recent investigations have validated the potential of reducing glutamine synthetase (GS) to inhibit neovascularization formation, offering prospects for treating variou...
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BMC
2024-11-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-024-02943-1 |
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| author | Miaomiao Zhang Xinyue Lu Lifu Luo Jinqiu Dou Jingbo Zhang Ge Li Li Zhao Fengying Sun |
| author_facet | Miaomiao Zhang Xinyue Lu Lifu Luo Jinqiu Dou Jingbo Zhang Ge Li Li Zhao Fengying Sun |
| author_sort | Miaomiao Zhang |
| collection | DOAJ |
| description | Abstract Choroidal neovascularization (CNV) is a leading cause of visual impairment in wet age-related macular degeneration (wAMD). Recent investigations have validated the potential of reducing glutamine synthetase (GS) to inhibit neovascularization formation, offering prospects for treating various neovascularization-related diseases. In this study, we devised a CRISPR/Cas9 delivery system employing the nucleic acid aptamer AS1411 as a targeting moiety and exosome-liposome hybrid nanoparticles as carriers (CAELN). Exploiting the binding affinity between AS1411 and nucleolin on endothelial cell surfaces, the delivery system was engineered to specifically target the glutamine synthetase gene (GLUL), thereby attenuating GS levels and continuously suppressing CNV. CAELN exhibited spherical and uniform dispersion. In vitro cellular investigations demonstrated gene editing efficiencies of CAELN ranging from 42.05 to 55.02% and its capacity to inhibit neovascularization in HUVEC cells. Moreover, in vivo pharmacodynamic studies conducted in CNV rabbits revealed efficacy of CAELN in restoring the thickness of intra- and extranuclear tissues. The findings suggest that GS is a novel target for the inhibition of pathological CNV, while the development of AS1411-modified exosome-liposome hybrid nanoparticles represents a novel delivery method for the treatment of neovascular-related diseases. |
| format | Article |
| id | doaj-art-0c5e976d45cf4377a4c68457a251f7f1 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-0c5e976d45cf4377a4c68457a251f7f12024-11-17T12:46:51ZengBMCJournal of Nanobiotechnology1477-31552024-11-0122111610.1186/s12951-024-02943-1Targeting glutamine synthetase with AS1411-modified exosome-liposome hybrid nanoparticles for inhibition of choroidal neovascularizationMiaomiao Zhang0Xinyue Lu1Lifu Luo2Jinqiu Dou3Jingbo Zhang4Ge Li5Li Zhao6Fengying Sun7Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin UniversityKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin UniversityDepartment of Ophthalmology, The Second Hospital of Jilin University, Jilin UniversityKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin UniversityKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin UniversityKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin UniversityKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin UniversityKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin UniversityAbstract Choroidal neovascularization (CNV) is a leading cause of visual impairment in wet age-related macular degeneration (wAMD). Recent investigations have validated the potential of reducing glutamine synthetase (GS) to inhibit neovascularization formation, offering prospects for treating various neovascularization-related diseases. In this study, we devised a CRISPR/Cas9 delivery system employing the nucleic acid aptamer AS1411 as a targeting moiety and exosome-liposome hybrid nanoparticles as carriers (CAELN). Exploiting the binding affinity between AS1411 and nucleolin on endothelial cell surfaces, the delivery system was engineered to specifically target the glutamine synthetase gene (GLUL), thereby attenuating GS levels and continuously suppressing CNV. CAELN exhibited spherical and uniform dispersion. In vitro cellular investigations demonstrated gene editing efficiencies of CAELN ranging from 42.05 to 55.02% and its capacity to inhibit neovascularization in HUVEC cells. Moreover, in vivo pharmacodynamic studies conducted in CNV rabbits revealed efficacy of CAELN in restoring the thickness of intra- and extranuclear tissues. The findings suggest that GS is a novel target for the inhibition of pathological CNV, while the development of AS1411-modified exosome-liposome hybrid nanoparticles represents a novel delivery method for the treatment of neovascular-related diseases.https://doi.org/10.1186/s12951-024-02943-1CRISPR/Cas9Choroidal neovascularizationExosomeLiposomeGlutamine synthetaseAge-related macular degeneration |
| spellingShingle | Miaomiao Zhang Xinyue Lu Lifu Luo Jinqiu Dou Jingbo Zhang Ge Li Li Zhao Fengying Sun Targeting glutamine synthetase with AS1411-modified exosome-liposome hybrid nanoparticles for inhibition of choroidal neovascularization Journal of Nanobiotechnology CRISPR/Cas9 Choroidal neovascularization Exosome Liposome Glutamine synthetase Age-related macular degeneration |
| title | Targeting glutamine synthetase with AS1411-modified exosome-liposome hybrid nanoparticles for inhibition of choroidal neovascularization |
| title_full | Targeting glutamine synthetase with AS1411-modified exosome-liposome hybrid nanoparticles for inhibition of choroidal neovascularization |
| title_fullStr | Targeting glutamine synthetase with AS1411-modified exosome-liposome hybrid nanoparticles for inhibition of choroidal neovascularization |
| title_full_unstemmed | Targeting glutamine synthetase with AS1411-modified exosome-liposome hybrid nanoparticles for inhibition of choroidal neovascularization |
| title_short | Targeting glutamine synthetase with AS1411-modified exosome-liposome hybrid nanoparticles for inhibition of choroidal neovascularization |
| title_sort | targeting glutamine synthetase with as1411 modified exosome liposome hybrid nanoparticles for inhibition of choroidal neovascularization |
| topic | CRISPR/Cas9 Choroidal neovascularization Exosome Liposome Glutamine synthetase Age-related macular degeneration |
| url | https://doi.org/10.1186/s12951-024-02943-1 |
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