Dopamine-melanin nanoparticles scavenge reactive oxygen and nitrogen species and activate autophagy for osteoarthritis therapy

Anti-oxidative agents hold great potential in osteoarthritis (OA) therapy. However, most radical scavengers have poor biocompatibility and potential cytotoxicity, which limit their applications. Herein we explore dopamine melanin (DM) nanoparticles as a novel scavenger of reactive oxygen species (RO...

Full description

Saved in:
Bibliographic Details
Published in:Nanoscale 2019-06, Vol.11 (24), p.1165-11616
Main Authors: Zhong, Gang, Yang, Xueyuan, Jiang, Xianfang, Kumar, Anil, Long, Huiping, Xie, Jin, Zheng, Li, Zhao, Jinmin
Format: Article
Language:English
Subjects:
Animals
Antioxidants
Arthritis
Autophagy
Biocompatibility
Biomedical materials
Cartilage
Cytotoxicity
Disease Models, Animal
Dopamine
Dopamine - chemistry
Dopamine - pharmacology
Female
Free Radical Scavengers - chemistry
Free Radical Scavengers - pharmacology
Hydroxyl radicals
Melanin
Melanins - chemistry
Melanins - pharmacology
Nanoparticles
Nanoparticles - chemistry
Nanoparticles - therapeutic use
Osteoarthritis - drug therapy
Osteoarthritis - metabolism
Osteoarthritis - pathology
Proteoglycans
Rats
Rats, Sprague-Dawley
Reactive Nitrogen Species - metabolism
Reactive Oxygen Species - metabolism
Therapy
Toxicity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Anti-oxidative agents hold great potential in osteoarthritis (OA) therapy. However, most radical scavengers have poor biocompatibility and potential cytotoxicity, which limit their applications. Herein we explore dopamine melanin (DM) nanoparticles as a novel scavenger of reactive oxygen species (ROS) and reactive nitrogen species (RNS). DM nanoparticles show low cytotoxicity and a strong ability to sequester a broad range of ROS and RNS, including superoxides, hydroxyl radicals, and peroxynitrite. This translates to excellent anti-inflammatory and chondro-protective effects by inhibiting intracellular ROS and RNS and promoting antioxidant enzyme activities. With an average diameter of 112.5 nm, DM nanoparticles can be intra-articularly (i.a.) injected into an affected joint and retained at the injection site. When tested in vivo in rodent OA models, DM nanoparticles showed diminished inflammatory cytokine release and reduced proteoglycan loss, which in turn slowed down cartilage degradation. Mechanistic studies suggest that DM nanoparticles also enhance autophagy that benefits OA control. In summary, our study suggests DM nanoparticles as a safe and promising therapeutic for OA. Anti-oxidative agents hold great potential in osteoarthritis (OA) therapy.
ISSN:2040-3364
2040-3372
DOI:10.1039/c9nr03060c