Language

English

Publication Date

8-8-2025

Journal

Science Advances

DOI

10.1126/sciadv.adw1358

PMID

40768585

PMCID

PMC12327454

PubMedCentral® Posted Date

8-6-2025

PubMedCentral® Full Text Version

Post-print

Abstract

This study investigates a dual-acting drug delivery system using naringenin (NAR) as a folate receptor ligand to enhance intestinal uptake and encapsulated NAR for combating inflammation. The dual-acting systems were tested in vitro on cisplatin-induced human kidney-2 cells and in vivo in a mouse model of cisplatin-induced acute kidney injury (AKI). NAR-loaded passive nanoparticles [P2Ns(NAR)] and dual-acting systems [P2Ns-NAR(NAR)] showed notable advantages over unformulated NAR, reducing the required dose by up to 57 and 79%, respectively. These nanoparticles modulated immune responses, restored T cell function, and shifted macrophage polarization from proinflammatory M1 to tissue-repairing M2. In addition, P2Ns-NAR(NAR) alleviated AKI by reducing fibrosis and lowering Toll-like receptor 4 and nuclear factor κB levels in the kidneys. Notably, P2Ns-NAR(NAR) outperformed other formulations, providing a 50% lower effective dose. This study emphasizes the potential of NAR to overcome intestinal barriers and highlights the importance of polymer functionality in delivering effective treatments for inflammatory diseases.

Keywords

Animals, Nanoparticles, Humans, Mice, Polyesters, Anti-Inflammatory Agents, Acute Kidney Injury, Disease Models, Animal, Cisplatin, Cell Line, Flavanones, Drug Delivery Systems, Macrophages, Toll-Like Receptor 4, Inflammation, Kidney, NF-kappa B

Published Open-Access

yes

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