Orange-derived extracellular vesicles nanodrugs for efficient treatment of ovarian cancer assisted by transcytosis effect  

作　　者：Feng Long Yao Pan Jinheng Li Suinan Sha Xiubo Shi Haoyan Guo Chuanqing Huang Qian Xiao Chao Fan Xingmei Zhang Jun-Bing Fan Ying Wang 

机构地区：[1]Cancer Research Institute,Experimental Education/Administration Center,Key Laboratory of Functional Proteomics of Guangdong Province,School of Basic Medical Sciences,Southern Medical University,Guangzhou 510515,China [2]Department of Neurobiology,School of Basic Medical Sciences,Southern Medical University,Guangzhou 510515,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第12期5121-5134,共14页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(22275080,22075127,and 82073340);the Natural Science Foundation of Guangdong Province(2022A 1515012044,China).

摘　　要：Extracellular vesicles(EVs)have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size,biocompatibility,and high stability.Herein,we demonstrate orange-derived extracellular vesicles(OEV)nanodrugs(DN@OEV)by modifying cRGD-targeted doxorubicin(DOX)nanoparticles(DN)onto the surface of OEV,enabling significantly enhancing tumor accumulation and penetration,thereby efficiently inhibiting the growth of ovarian cancer.The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells,which presented the average above 10-fold transcytosis effect compared with individual DN.It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway,thereby inducing the enhanced transcytosis.In particular,the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process.Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of thedrugdelivery system.

关 键 词：Extracellular vesicles TRANSCYTOSIS Cancer treatment Drug delivery system Targeted modification Receptor-mediated endocytosis Intracellular trafficking Recycling endosome 

分 类 号：R73[医药卫生—肿瘤]