Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation.

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

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Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation.

Author: Weiyi XIA ¹ ; Chao LI ² ; Qinjun CHEN ² ; Jiancheng HUANG ¹ ; Zhenhao ZHAO ² ; Peixin LIU ² ; Kai XU ¹ ; Lei LI ¹ ; Fangyuan HU ¹ ; Shujie ZHANG ¹ ; Tao SUN ² ; Chen JIANG ² ; Chen ZHAO ¹
Author Information

1. Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, China.
2. Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.
Publication Type:Journal Article
Keywords: Age-related macular degeneration; Biomimetic nanoparticles; Choroidal neovascularization; Inflammation; Macrophage membrane; Rapamycin; Targeted drug delivery; mTOR signaling
From: Acta Pharmaceutica Sinica B 2022;12(5):2506-2521
CountryChina
Language:English
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.