Insulin-incubated palladium clusters promote recovery after brain injury

Abstract

Traumatic brain injury (TBI) is a cause of disability and death worldwide, but there are currently no specific treatments for this condition. Release of excess reactive oxygen species (ROS) in the injured brain leads to a series of pathological changes; thus, eliminating ROS could be a potential therapeutic strategy. Herein, we synthesized insulin-incubated ultrasmall palladium (Pd@insulin) clusters via green biomimetic chemistry. The Pd@insulin clusters, which were 3.2 nm in diameter, exhibited marked multiple ROS-scavenging ability testified by the theoretical calculation. Pd@insulin could be rapidly excreted via kidney-urine metabolism and induce negligible adverse effects after a long-time treatment in vivo. In a TBI mouse model, intravenously injected Pd@insulin clusters aggregated in the injured cortex, effectively suppressed excessive ROS production, and significantly rescued motor function, cognition and spatial memory. We found that the positive therapeutic effects of the Pd@insulin clusters were mainly attributed to their ROS-scavenging ability, as they inhibited excessive neuroinflammation, reduced cell apoptosis, and prevented neuronal loss. Therefore, the ability of Pd@insulin clusters to effectively eliminate ROS, as well as their simple structure, easy synthesis, low toxicity, and rapid metabolism may facilitate their clinical translation for TBI treatment.

Recent Advances in Biomaterials‐Based Therapies for Alleviation and Regeneration of Traumatic Brain Injury

“…The decrease of ROS/RNS promotes neuronal survival, alleviates neuroinflammation, and improves outcome of severe TBI. [52] There are three main methods for the adaptive biomaterials to accomplish the property of ROS scavenging, that is, polymers with ROS-responsive units (mainly thioether [53][54][55][56][57] for TBI), biomaterials loaded with bioactive small molecules (e.g., gallic acid (GA), [58] evodiamine, [59,60] procyanidins, [61] and curcumin [53,62] ), and nanozymes that mimic nature enzyme activity (for example, palladium clusters, [63] cerium oxide nanoparticles, [64] and carbon dots (CDs) [65][66][67][68] ). [48] Copyright 2020, Elsevier.…”

“…[71,72] Fu et al synthesized Pd@insulin nanoparticles as the mimic of superoxide dismutase (SOD) and catalase (CAT) to ease inflammatory responses and oxidative stress after TBI. [63] The insulin promotes the crossing of nano-enzymes through BBB via receptor-mediated transcytosis.…”

Insulin‐incubated palladium clusters alleviate Alzheimer's disease‐like phenotypes in a preclinical mouse model

“… 1 Generally, there are two common types of ROS scavengers, natural enzymes and antioxidant drugs. 2 , 3 However, they have not been applied for AD therapeutics yet due to high cost, low stability, difficulty of recycling, and limited scavenging capacity for multiple types of ROS. Inspiringly, nanozymes, the nanomaterials for mimicking the catalytic properties of natural enzymes, have emerged as excellent substitutes for ROS natural scavengers as they are more stable, durable, and cost‐friendly than natural enzymes and antioxidant drugs.…”

“…Inspiringly, nanozymes, the nanomaterials for mimicking the catalytic properties of natural enzymes, have emerged as excellent substitutes for ROS natural scavengers as they are more stable, durable, and cost‐friendly than natural enzymes and antioxidant drugs. 2 , 3 Nanozymes therefore have been reported to facilitate the technological innovations of biomedicine, including the development of nanomaterials with multi‐biofunctions for tissue engineering, neurodegenerative diseases, cancer therapy, and disease diagnosis. 4 Nanozymes can be further decorated/modified with polymer, protein, or cell membrane to protect their catalytic activities and improve their stability and biocompatibility for biological applications.…”

“…Recently, we reported the synthesis of an ultrasmall insulin‐incubated palladium nanozyme Pd@insulin (Pd‐In), via a novel biomimetic synthesis method. 2 This method utilizes the spatial confinement effect and protein‐mediated biomimetic biomineralization, which is convenient, green, and highly effective. Pd‐based nanozyme was chosen due to its specific electronic structure that mimics the catalytic properties of natural enzymes.…”