pH-sensitive cationic nanoparticles for endosomal cell-free DNA scavenging against acute inflammation

Copyright © 2024 Elsevier B.V. All rights reserved..

Cell-free DNA (cfDNA) released from dead cells could be a player in some autoimmune disorders by activating Toll-like receptor 9 (TLR9) and inducing proinflammatory cytokines. Cationic nanoparticles (cNPs) address cfDNA clearance, yet challenges persist, including toxicity, low specificity and ineffectiveness against endocytosed cfDNA. This study introduced pH-sensitive cNPs, reducing off-target effects and binding cfDNA at inflammatory sites. This unique approach inhibits the TLR9 pathway, offering a novel strategy for inflammation modulation. Synthesized cNPs, with distinct cationic moieties, exhibit varied pKa values, enhancing cfDNA binding. Comprehensive studies elucidate the mechanism, demonstrating minimal extracellular binding, enhanced endosomal DNA binding, and optimal tumor necrosis factor-α suppression. In a traumatic brain injury mice model, pH-sensitive cNPs effectively suppress inflammatory cytokines, highlighting their potential in acute inflammation regulation.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:369

Enthalten in:

Journal of controlled release : official journal of the Controlled Release Society - 369(2024) vom: 25. März, Seite 88-100

Sprache:

Englisch

Beteiligte Personen:

Feng, Yilin [VerfasserIn]
Wei, Cong [VerfasserIn]
Gu, Yanrong [VerfasserIn]
Zhang, Hong [VerfasserIn]
Liu, Lixin [VerfasserIn]
Chen, Yongming [VerfasserIn]
Zhao, Tianyu [VerfasserIn]

Links:

Volltext

Themen:

Cationic nanoparticles
Inflammation regulation
Journal Article
PH-sensitive
Polycaprolactone

Anmerkungen:

Date Revised 26.03.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1016/j.jconrel.2024.03.003

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369613570