Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation
Retinal pigment epithelial (RPE) is primarily impaired in age-related macular degeneration (AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization (CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor, rapam...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-05-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383521004251 |
| _version_ | 1818211806496161792 |
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| author | Weiyi Xia Chao Li Qinjun Chen Jiancheng Huang Zhenhao Zhao Peixin Liu Kai Xu Lei Li Fangyuan Hu Shujie Zhang Tao Sun Chen Jiang Chen Zhao |
| author_facet | Weiyi Xia Chao Li Qinjun Chen Jiancheng Huang Zhenhao Zhao Peixin Liu Kai Xu Lei Li Fangyuan Hu Shujie Zhang Tao Sun Chen Jiang Chen Zhao |
| author_sort | Weiyi Xia |
| collection | DOAJ |
| description | Retinal pigment epithelial (RPE) is primarily impaired in age-related macular degeneration (AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization (CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor, rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages (termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD. |
| first_indexed | 2024-12-12T05:38:21Z |
| format | Article |
| id | doaj.art-919a3ed225d447b4bb3089cceaba262b |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-12T05:38:21Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-919a3ed225d447b4bb3089cceaba262b2022-12-22T00:36:01ZengElsevierActa Pharmaceutica Sinica B2211-38352022-05-0112525062521Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulationWeiyi Xia0Chao Li1Qinjun Chen2Jiancheng Huang3Zhenhao Zhao4Peixin Liu5Kai Xu6Lei Li7Fangyuan Hu8Shujie Zhang9Tao Sun10Chen Jiang11Chen Zhao12Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaDepartment of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaDepartment of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, ChinaDepartment of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, ChinaDepartment of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, ChinaDepartment of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China; Corresponding authors. Fax: +86 21 64377134 (Chen Zhao), +86 21 51980079 (Chen Jiang).Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, China; Corresponding authors. Fax: +86 21 64377134 (Chen Zhao), +86 21 51980079 (Chen Jiang).Retinal pigment epithelial (RPE) is primarily impaired in age-related macular degeneration (AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization (CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor, rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages (termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.http://www.sciencedirect.com/science/article/pii/S2211383521004251Choroidal neovascularizationAge-related macular degenerationBiomimetic nanoparticlesTargeted drug deliverymTOR signalingRapamycin |
| spellingShingle | Weiyi Xia Chao Li Qinjun Chen Jiancheng Huang Zhenhao Zhao Peixin Liu Kai Xu Lei Li Fangyuan Hu Shujie Zhang Tao Sun Chen Jiang Chen Zhao Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation Acta Pharmaceutica Sinica B Choroidal neovascularization Age-related macular degeneration Biomimetic nanoparticles Targeted drug delivery mTOR signaling Rapamycin |
| title | Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation |
| title_full | Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation |
| title_fullStr | Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation |
| title_full_unstemmed | Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation |
| title_short | Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation |
| title_sort | intravenous route to choroidal neovascularization by macrophage disguised nanocarriers for mtor modulation |
| topic | Choroidal neovascularization Age-related macular degeneration Biomimetic nanoparticles Targeted drug delivery mTOR signaling Rapamycin |
| url | http://www.sciencedirect.com/science/article/pii/S2211383521004251 |
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