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Article Dans Une Revue Biomaterials Science Année : 2023

Cationic phosphorus dendron nanomicelles deliver microRNA mimics and microRNA inhibitors for enhanced anti-inflammatory therapy of acute lung injury

Résumé

The development of efficient nanomedicines to repress the repolarization of M1 phenotype macrophages and therefore inhibit pro-inflammatory cytokine overexpression for anti-inflammatory therapy is still a challenging task. We report here an original gene delivery nanoplatform based on pyrrolidinium-modified amphiphilic generation 1 phosphorus dendron (C12G1) nanomicelles with a rigid phosphorous dendron structure. The nanomicelles display higher gene delivery efficiency than the counterpart materials of pyrrolidinium-modified G1 phosphorus dendrimers, and meanwhile exhibit excellent cytocompatibility. The C12G1 nanomicelles can be employed to co-deliver the miRNA-146a mimic (miR-146a mimic) and miRNA-429 inhibitor (miR-429i) to inhibit the Toll-like receptor-4 signaling pathway and p38 mitogen-activated protein kinase signaling pathway, respectively, thus causing repression of M1 phenotype alveolar macrophage polarization. The developed C12G1/miR-mixture polyplexes enable efficient therapy of lipopolysaccharide-activated alveolar macrophages in vitro and an acute lung injury mouse model in vivo. The generated cationic phosphorus dendron nanomicelles may hold promising potential for anti-inflammatory gene therapy of other inflammatory diseases.
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Dates et versions

hal-04175366 , version 1 (02-08-2023)

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Jin Li, Liang Chen, Huxiao Sun, Mengsi Zhan, Regis Laurent, et al.. Cationic phosphorus dendron nanomicelles deliver microRNA mimics and microRNA inhibitors for enhanced anti-inflammatory therapy of acute lung injury. Biomaterials Science, 2023, 11 (4), pp.1530-1539. ⟨10.1039/D2BM01807A⟩. ⟨hal-04175366⟩
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