ArticleEMBO molecular medicine2021
Targeted delivery of a phosphoinositide 3-kinase γ inhibitor to restore organ function in sepsis.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Extrahepatic Gene Editing In Vivo Using Organic Solvent-Free Lipid Nanoparticles.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Attenuation of Ventilation-Induced Endoplasmic Reticulum Stress Associated with Lung Injury Through Phosphoinositide 3-Kinase-Gamma in a Murine Endotoxemia Model.International journal of molecular sciences · 2025Article
- Gut Microbiota and Liver Dysfunction in Sepsis: The Role of Inflammatory Mediators and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Compartmentalization of the inflammatory response during bacterial sepsis and severe COVID-19.Journal of intensive medicine · 2024Review
- Metamizole outperforms meloxicam in sepsis: insights on analgesics, survival and immunomodulation in the peritoneal contamination and infection sepsis model.Frontiers in immunology · 2024Article
- Immunosuppressive effects of circulating bile acids in human endotoxemia and septic shock: patients with liver failure are at risk.Critical care (London, England) · 2023Article
- Raman Spectroscopy Profiling of Splenic T-Cells in Sepsis and Endotoxemia in Mice.International journal of molecular sciences · 2023Article
- RIPK3 promoter hypermethylation in hepatocytes protects from bile acid-induced inflammation and necroptosis.Cell death & disease · 2023Article
- The liver in sepsis: molecular mechanism of liver failure and their potential for clinical translation.Molecular medicine (Cambridge, Mass.) · 2022Review
- Automated multicolor mesoscopic imaging for the 3-dimensional reconstruction of fluorescent biomarker distribution in large tissue specimens.Biomedical optics express · 2022Article
- Targeted delivery of a phosphoinositide 3-kinase γ inhibitor to restore organ function in sepsis.EMBO molecular medicine · 2021Article
- Hormesis Meetings at the Royal Palace.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Jaundice, the clinical hallmark of infection-associated liver dysfunction, reflects altered membrane organization of the canalicular pole of hepatocytes and portends poor outcomes. Mice lacking phosphoinositide 3-kinase-γ (PI3Kγ) are protected against membrane disintegration and hepatic excretory dysfunction. However, they exhibit a severe immune defect that hinders neutrophil recruitment to sites of infection. To exploit the therapeutic potential of PI3Kγ inhibition in sepsis, a targeted approach to deliver drugs to hepatic parenchymal cells without compromising other cells, in particular immune cells, seems warranted. Here, we demonstrate that nanocarriers functionalized through DY-635, a fluorescent polymethine dye, and a ligand of organic anion transporters can selectively deliver therapeutics to hepatic parenchymal cells. Applying this strategy to a murine model of sepsis, we observed the PI3Kγ-dependent restoration of biliary canalicular architecture, maintained excretory liver function, and improved survival without impairing host defense mechanisms. This strategy carries the potential to expand targeted nanomedicines to disease entities with systemic inflammation and concomitantly impaired barrier functionality.
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