Penumbra-targeted CircOGDH siRNA-loaded nanoparticles alleviate neuronal apoptosis in focal brain ischaemia  

作　　者：Yanfang Liu Tianyuan Zhang Xing Zou Zhongwen Yuan Yufeng Li Jiankun Zang Niu He Lizhen He Anding Xu Dan Lu 

机构地区：[1]Department of Neurology and Stroke Center,Jinan University First Affiliated Hospital,Guangzhou,Guangdong,China [2]Department of Clinical Neuroscience Institute,The First Affiliated Hospital of Jinan University,Guangzhou,Guangdong,China [3]Key Lab of Guangzhou Basic and Translational Research of Pan-vascular Diseases,The First Affiliated Hospital of Jinan University,Guangzhou,China

出　　处：《Stroke & Vascular Neurology》2024年第2期134-144,I0396-I0413,共29页卒中与血管神经病学（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(81801150,81971121,82271304,82171316 and 81671167);the Science and Technology Planning Project of Guangdong Province,China(2017A020215049 and 2019A050513005);Natural Science Foundation of Guangdong Province(2018A0303130182,2020A1515010279 and 2022A1515012311);the Fundamental Research Funds for the Central Universities(21621102);Science and Technology Projects in Guangzhou,China(2014Y2-00505,202002020003,202201010127 and 202201020042);Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,China(JNU1AF-CFTP-2022-a01203).

摘　　要：Background Nanoparticles(NPs)are a class of substances that can be loaded with therapeutic agents delivered to specific areas.In our earlier research,we identified a neuron-derived circular RNA(circRNA),circular oxoglutarate dehydrogenase(CircOGDH),as a promising therapeutic target for acute ischaemic stroke.This study dedicated to explore a prospective preliminary strategy of CircOGDH-based NP delivered to the ischaemic penumbra region in middle cerebral artery occlusion/reperfusion(MCAO/R)mice.Methods Immunofluorescence in primary cortex neurons and in vivo fluorescence imaging revealed endocytosis of Poly(lactide-co-glycolide)(PLGA)poly amidoamine(PAMAM)@CircOGDH small interfering RNA(siRNA)NPs.Western blotting analysis and CCK8 assay were performed to evaluate the apoptotic level in ischaemic neurons treated with PLGA–PAMAM@CircOGDH siRNA NPs.Quantitative reverse transcription PCR experiments,mice behaviour test,T2 MRI analysis,Nissl and TdT-mediated dUTP nick end labeling(TUNEL)co-staining were performed to evaluate the apoptosis level of ischaemic penumbra neurons in MCAO/R mice.Biosafety evaluation of NPs in MCAO/R mice was detected by blood routine examination,liver and kidney function examination and HE staining.Results PLGA–PAMAM@CircOGDH siRNA NPs were successfully assembled.Endocytosis of PLGA–PAMAM@CircOGDH siRNA NPs in ischaemic neurons alleviated neuronal apoptotic level in vitro and in vivo.Furthermore,mice behaviour test showed that the neurological defects of MCAO/R mice were significantly alleviated after the tail injection of PLGA–PAMAM@CircOGDH siRNA NPs,and no toxic effects were observed.Conclusion In conclusion,our results suggest that PLGA–PAMAM@CircOGDH siRNA NPs can be delivered to the ischaemic penumbra region and alleviate neuron apoptosis in MCAO/R mice and in ischaemic neurons;therefore,our study provides a desirable approach for using circRNA-based NPs for the treatment of ischaemic stroke.

关 键 词：OGD ROUTINE loaded 

分 类 号：R743.3[医药卫生—神经病学与精神病学]