PT  - JOURNAL ARTICLE
AU  - Liu, Yanfang
AU  - Zhang, Tianyuan
AU  - Zou, Xing
AU  - Yuan, Zhongwen
AU  - Li, Yufeng
AU  - Zang, Jiankun
AU  - He, Niu
AU  - He, Lizhen
AU  - Xu, Anding
AU  - Lu, Dan
TI  - Penumbra-targeted CircOGDH siRNA-loaded nanoparticles alleviate neuronal apoptosis in focal brain ischaemia
AID  - 10.1136/svn-2022-002009
DP  - 2024 Apr 01
TA  - Stroke and Vascular Neurology
PG  - 134--144
VI  - 9
IP  - 2
4099  - http://svn.bmj.com/content/9/2/134.short
4100  - http://svn.bmj.com/content/9/2/134.full
SO  - Stroke Vasc Neurol2024 Apr 01; 9
AB  - 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.All data relevant to the study are included in the article or uploaded as supplemental information.