Peptide-mediated targeted delivery of SOX9 nanoparticles into astrocytes ameliorates ischemic brain injury

Shin, Hyo Jung; Choi, Seung Gyu; Qu, Fengrui; Yi, Min-Hee; Lee, Choong-Hyun; Kim, Sang Ryong; Kim, Hyeong-Geug; Beom, Jaewon; Yi, Yoonyoung; Kim, Do Kyung; Joe, Eun-Hye; Song, Hee-Jung; Kim, Yonghyun; Kim, Dong Woon

doi:10.1039/d3nr01318a

Nanoscale

2024

DOI: 10.1039/d3nr01318a

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Peptide-mediated targeted delivery of SOX9 nanoparticles into astrocytes ameliorates ischemic brain injury

Hyo Jung Shin,

Seung Gyu Choi,

Fengrui Qu

et al.

Abstract: We describes the development of a poly-lactic-coglycolic acid (PLGA) nanoparticle-based system for conjugation of targeting peptides to PLGA nanoparticles and delivery of the therapeutic gene SOX9 to damaged astrocytes in a mouse stroke model.

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Cited by 2 publications

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Nanomaterials for stroke diagnosis and treatment

Liu,

Li,

Guo

et al. 2024

iScience

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Nanomaterials for stroke diagnosis and treatment

Liu,

Li,

Guo

et al. 2024

iScience

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Rejuvenating aged microglia by p16ink4a-siRNA-loaded nanoparticles increases amyloid-β clearance in animal models of Alzheimer’s disease

Shin,

Kim,

Choi

et al. 2024

Mol Neurodegeneration

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Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer’s disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance. First, we used gene ontology analysis of microglia from young and old mice to identify differential expression of cyclin-dependent kinase inhibitor 2A (p16ink4a), a cell cycle factor related to aging. We found that p16ink4a expression was increased in microglia near amyloid plaques in brain tissue from patients with AD and 5XFAD mice, a model of AD. In BV2 microglia, small interfering RNA (siRNA)-mediated p16ink4a downregulation transformed microglia with enhanced amyloid phagocytic capacity through regulated the cell cycle and increased cell proliferation. To regulate microglial phagocytosis by gene transduction, we used poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles, which predominantly target microglia, to deliver the siRNA and to control microglial reactivity. Nanoparticle-based delivery of p16ink4a siRNA reduced amyloid plaque formation and the number of aged microglia surrounding the plaque and reversed learning deterioration and spatial memory deficits. We propose that downregulation of p16ink4a in microglia is a promising strategy for the treatment of Alzheimer’s disease.

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Peptide-mediated targeted delivery of SOX9 nanoparticles into astrocytes ameliorates ischemic brain injury

Abstract: We describes the development of a poly-lactic-coglycolic acid (PLGA) nanoparticle-based system for conjugation of targeting peptides to PLGA nanoparticles and delivery of the therapeutic gene SOX9 to damaged astrocytes in a mouse stroke model.

Cited by 2 publications

References 52 publications

Nanomaterials for stroke diagnosis and treatment

Nanomaterials for stroke diagnosis and treatment

Rejuvenating aged microglia by p16ink4a-siRNA-loaded nanoparticles increases amyloid-β clearance in animal models of Alzheimer’s disease

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