Polydopamine nanoparticles as dual-task platform for osteoarthritis therapy: A scavenger for reactive oxygen species and regulator for cellular powerhouses

Because of the obscure etiology of osteoarthritis (OA) and unsatisfactory treatment outcomes, new effective and minimally invasive therapies are urgently needed. Oxidative stress elicited by excessive reactive oxygen species (ROS) accumulation has historically been considered a potential trigger of OA. Polydopamine (PDA), an emerging versatile biopolymer produced by self-polymerization of dopamine, has attracted considerable attention in biomedical applications by virtue of its excellent biocompatibility and intriguing ROS-scavenging capacity. Herein, an antioxidative/anti-inflammatory dual-task nanoplatform based on PDA nanoparticles (NPs) is introduced for the treatment of temporomandibular joint osteoarthritis (TMJ-OA). In addition to directly reacting with ROS as a reducing agent, PDA NPs also regulate ROS generation in mitochondria which are considered cellular powerhouses. Specifically, the efficiency of mitochondrial oxidative phosphorylation (OXPHOS) is significantly increased in the presence of PDA NPs, indicating that PDA NPs may increase the efficiency of mitochondrial respiration, hence reducing ROS production. This intriguing dual-antioxidative mechanism may account for the remarkable antioxidative capacity of PDA NPs. Moreover, the anti-inflammatory capacity of PDA NPs is revealed both in vitro and in vivo. This work not only opens a new avenue for OA treatment but also provides valuable insights into the design of biomaterials with multiple biomedical applications via regulation of cellular energy metabolism.