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Updated: Sep 21, 2025
In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal Neovascularization Model
Published on: January 21, 2018
Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation
Weiyi Xia1, Chao Li2, Qinjun Chen2
1Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, China.
Abstract:
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.
Insights
Biomimetic nanocomplexes loaded with rapamycin and coated in macrophage membranes (MRaNPs) effectively target age-related macular degeneration lesions. This approach enhances rapamycin delivery, downregulates the mTOR pathway, and promotes RPE autophagy for therapeutic benefit.
Area of Science:
- Ophthalmology and Regenerative Medicine
- Nanotechnology and Biomaterials
Background:
- Age-related macular degeneration (AMD) involves retinal pigment epithelial (RPE) cell damage, leading to photoreceptor loss and choroidal neovascularization (CNV).
- The mechanistic target of rapamycin (mTOR) pathway is implicated in AMD pathogenesis, but rapamycin's therapeutic use is limited.
- Developing targeted, noninvasive therapies is crucial for AMD treatment.
Purpose of the Study:
- To develop a novel biomimetic nanocarrier system for targeted delivery of rapamycin to AMD lesions.
- To investigate the efficacy of macrophage-membrane-coated rapamycin nanoparticles (MRaNPs) in modulating the mTOR pathway and treating AMD.
- To evaluate the potential of MRaNPs in activating autophagy and rescuing RPE cells.
Main Methods:
- Rapamycin-loaded nanoparticles were engineered and coated with cell membranes derived from macrophages to create MRaNPs.
- The biodistribution and accumulation of MRaNPs were assessed after intravenous injection, focusing on CNV lesions.
- The effects of MRaNPs on mTOR pathway downregulation, angiogenesis inhibition, and RPE autophagy activation were evaluated.
Main Results:
- Intravenous administration of MRaNPs demonstrated enhanced accumulation in CNV lesions due to macrophage membrane properties.
- MRaNPs effectively downregulated the mTOR pathway and attenuated angiogenesis in the eye.
- MRaNPs significantly activated autophagy in RPE cells, suggesting a protective mechanism against damage.
Conclusions:
- Macrophage-disguised rapamycin nanocarriers (MRaNPs) represent a promising noninvasive therapeutic strategy for AMD.
- Biomimetic cell membrane coating enhances targeted drug delivery and therapeutic efficacy for retinal diseases.
- MRaNPs offer a dual therapeutic approach by inhibiting angiogenesis and promoting RPE survival through autophagy.
