Intracellular codelivery of anti-inflammatory drug and anti-miR 155 to treat inflammatory disease  

作　　者：Chao Teng Chenshi Lin Feifei Huang Xuyang Xing Shenyu Chen Ling Ye Helena S.Azevedo Chenjie Xu Zhengfeng Wu Zhongjian Chen Wei He 

机构地区：[1]School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China [2]School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China [3]School of Engineering and Materials Science,Institute of Bioengineering,University of London,London E14NS,UK [4]Department of Biomedical Engineering,City University of Hong Kong,Kowloon,Hong Kong,China [5]Key Laboratory of Modern Preparation of TCM,Ministry of Education,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China [6]Shanghai Skin Disease Hospital,Tongji University School of Medicine,Shanghai 200443,China

出　　处：《Acta Pharmaceutica Sinica B》2020年第8期1521-1533,共13页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81872823 and 81773826);the Double First-Class(CPU2018PZQ13,China)of the China Pharmeutical University;the Ministry of Science and Technology of China(2018ZX09711001);the Shanghai Science and Technology Committee(19430741500,China);the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of traditional Chinese Medicine(TCM201905,China)

摘　　要：Atherosclerosis(AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein,targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy(drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals,named as baicalein nanorods(BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors in vitro and in vivo. In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.

关 键 词：miR155 INFLAMMATORY SUSTAINED 

分 类 号：R96[医药卫生—药理学]