Tudor domain-containing protein 9-targeting siRNA nanoparticles alleviate Pseudomonas aeruginosa lung injury in preclinical models by promoting neutrophil cuproptosis.
1/5 보강
Pseudomonas aeruginosa pneumonia poses a significant therapeutic challenge.
APA
Zhang W, Li H, et al. (2026). Tudor domain-containing protein 9-targeting siRNA nanoparticles alleviate Pseudomonas aeruginosa lung injury in preclinical models by promoting neutrophil cuproptosis.. Nature communications, 17(1). https://doi.org/10.1038/s41467-026-70349-8
MLA
Zhang W, et al.. "Tudor domain-containing protein 9-targeting siRNA nanoparticles alleviate Pseudomonas aeruginosa lung injury in preclinical models by promoting neutrophil cuproptosis.." Nature communications, vol. 17, no. 1, 2026.
PMID
41792170 ↗
Abstract 한글 요약
Pseudomonas aeruginosa pneumonia poses a significant therapeutic challenge. Nanoparticles serve as an effective tool for nucleic acid delivery to efficiently alleviate pneumonia. This study develops a hyaluronic acid (HA)-coated peptide nanoparticle system for targeted delivery of small interfering RNA (siRNA) against Tudor domain-containing protein 9 (TDRD9), identified via RNA sequencing of bronchoalveolar lavage fluid-derived neutrophils from 21 recruited patients (11 males/10 females). Adoptive transfer of TDRD9-silenced polymorphonuclear neutrophils into neutrophil-depleted male mice attenuates lung inflammation and edema. Mechanistically, TDRD9 suppresses neutrophil cuproptosis by upregulating programmed death ligand 1 (PD-L1) through interaction with CD80 to activate p38 mitogen-activated protein kinase (MAPK) signaling. HA-si-TDRD9 nanoparticles enhance neutrophil cuproptosis, reduce pulmonary neutrophil accumulation, and ameliorate lung injury via PD-L1/CD80/MAPK. Importantly, HA-si-TDRD9 nanoparticles reduce bacterial growth, apoptosis, and inflammation in human lung organoids. This work demonstrates that targeting TDRD9 with siRNA nanoparticle platform presents a promising therapeutic strategy for treating bacterial lung injury.
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