Therapy of spinal cord injury by zinc pyrogallol modified nanozyme via anti-inflammatory strategies

Abstract

ROS-mediated treatment is a potential strategy that can reduce the risk of spinal cord injury (SCI)-related obvious adverse effects, but at the cost of therapeutic efficacy. Considering the significant reactive oxygen species (ROS) scavenging ability and biocompatibility of natural enzyme such as superoxide dismutase (SOD) and catalase (CAT), zinc pyrogallol nanozyme (PA-Zn) was developed to treat the injured spinal cord, in which zinc as metal center was coupled to pyrogallol through the Zn-O-C bridge to form a zinc four-coordination structure that can mimic enzyme-like behaviors of SOD and CAT for SCI treatment. In vitro tests demonstrated that PA-Zn could efficiently inhibit the expression of ROS and M1-related markers (IL-1β), and upregulate the expression of M2-related markers (Arg-1). Furthermore, PA-Zn could significantly promote ventral horn neurons survival and locomotor functional recovery in vivo, while inhibit injured spinal cord damage, and decrease the infiltration of macrophages in the lesion. PA-Zn had a better therapeutic effect on SCI animals at extremely low dosage (0.1 mg kg−1) and shorter time (2 weeks). The working dosage of PA-Zn was even 100-fold lower than some previous reported nanomedicines for SCI treatment. The PA-Zn with muti-enzymatic activities and biocompatibility showed reliable and efficient treatment efficiency for not only SCI but also other ROS-mediated diseases.