Reactive oxygen species-scavenging nanoparticles coated with chondroitin sulfate protect cartilage against osteoarthritis in vivo
Zhaoyi Wang, Hao Xiong, Zihe Zhai, Yuejun Yao, Tong Zhou, Haolan Zhang, Cunyi Fan, Changyou Gao
Abstract
Osteoarthritis (OA) is a prevalent chronic inflammatory disease in joints. Current interventions confront systemic toxicity and insufficient bioavailability. The unbalanced microenvironment of OA joints mainly fosters over-expressed reactive oxygen species (ROS), extracellular matrix disintegration, and apoptosis of chondrocytes. In this study, a kind of ROS-scavenging, biodegradable and drug-free nanoparticles (PP NPs) were constructed by the crosslinking of poly(propylene fumarate) (PPF) and ROS-scavenging poly(thioketal) (PTK). The high content of PTK and high crosslinking density of PPF and PTK innovatively endowed the NPs with slow degradation and prolonged ROS-elimination ability. The NPs were further surface-modified with chondroitin sulfate (CS), one of the dietary supplements for osteoarthritis. The intrinsic properties of resultant PP-CS NPs were excavated in vitro and in vivo. The PP-CS NPs could desirably consume 1,10-diphenyl-2-picrylhydrazyl (DPPH) radicals without toxicity to RAW264.7 cells in vitro. With an average diameter of ∼ 300 nm, the PP-CS NPs could be intra-articular administrated in OA rats and showed prolonged joint retention time, allowing only one injection per month. Moreover, the PP-CS NPs possessed a prolonged ROS depletion and M2 macrophage induction effect, down-regulated inflammatory cytokines, and reduced glycosaminoglycans loss. Consequently, the PP-CS NPs protected articular surface erosion, inhibited uneven cartilage matrix, and attenuated OA progression.