Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation
巨噬细胞伪装纳米载体用于 mTOR 调节的脉络膜新生血管静脉途径
mTOR変調のためのマクロファージ偽装ナノキャリアによる脈絡膜血管新生への静脈内経路
mTOR 변조를 위한 대식세포로 위장한 나노운반체에 의한 맥락막 혈관신생에 대한 정맥내 경로
Vía intravenosa a la neovascularización coroidea mediante nanoportadores disfrazados de macrófagos para la modulación de mTOR
Voie intraveineuse vers la néovascularisation choroïdienne par des nanoporteurs déguisés en macrophages pour la modulation mTOR
Внутривенный путь к хориоидальной неоваскуляризации с помощью замаскированных макрофагами наноносителей для модуляции mTOR
Weiyi Xia ¹, Chao Li 李潮 ², Qinjun Chen 陈钦俊 ², Jiancheng Huang ¹, Zhenhao Zhao 赵振浩 ², Peixin Liu 刘沛鑫 ², Kai Xu ¹, Lei Li ¹, Fangyuan Hu 胡方圆 ¹, Shujie Zhang 章淑杰 ¹, Tao Sun 孙涛 ², Chen Jiang 蒋晨 ², Chen Zhao 赵晨 ¹
¹ Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, China
中国 上海 复旦大学附属眼耳鼻喉科医院
² Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China
中国 上海 复旦大学药学院 药剂学 智能化递药教育部重点实验室
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.
