Construction Of Specific Oxygenated Groups Enriched Nanocarbons For Biomedical Applications

Owing to their unique physiochemical properties and high biocompatibility,carbon-based nanomaterials(nanocarbons)have aroused great attention in biomedical fields.Recently,the reactive oxygen species(ROS)-regulating properties of nanocarbons have been explored under physiological and pathological conditions for treating various diseases.However,the relatively low activities and unclear chemical mechanisms of nanocarbons during redox regulation greatly limit their practical usages.Herein,exhaustive characterizations of the ROS-regulating properties of nanocarbons have been provided by investigating the accurate effect of various surface oxygenated groups.Meanwhile,a series of specific oxygenated groups enriched nanocarbons were designed for biomedical applications including bacterial infections treatment and antioxidative therapy.In addition,a novel activatable nanoprobe was developed for in vivo monitoring ROS levels via magnetic resonance imaging(MRI).The main results are summarized as follows:1.Carbon nanotubes(CNTs)have been used as metal-free nanozymes to mimic the function of natural enzymes.However,the relatively low enzymatic activity usually limits their biomedical usages.Herein,we develop several oxygenated groups enriched carbon nanotubes(o-CNTs)as high-efficacy peroxidase mimics.Exhaustive mechanistic investigations indicated that carbonyl groups on o-CNTs were the active sites,whereas carbonxyl groups and hydroxyl groups served as competitive sites and inhibited the catalytic process,respectively.Moreover,2-bromo-1-phenylethanone modified o-CNTs(o-CNTs-BrPE)with higher peroxidase-like activity were further prepared via deactivating the competitive sites on o-CNTs.Results of both in vitro and in vivo nanozyme-mediated bacterial clearance demonstrated the feasibility of o-CNTs-BrPE as efficient peroxidase mimics to enhance the generation of ROS under physiological conditions,and protect the wound from bacteria-triggered edema and inflammation.2.The excess generation of ROS in kidneys during acute kidney injury(AKI)has been considered as a major cause of renal failure.Currently available antioxidants for AKI treatment often lack required antioxidative efficacy or renal accumulation rate.Herein,inspired by the structure of natural phenolic antioxidants,phenol-like group functionalized graphene quantum dots(h-GQDs)with both high ROS scavenging efficacy and renal specificity are constructed for AKI antioxidative therapy.Similar to natural polyphenols,the abundant phenol-like groups on h-GQDs are demonstrated to be the active components to exert antioxidative effects.Exhaustive characterizations of the antioxidative activity of h-GQDs demonstrate that their ultrahigh antioxidative activity originates not solely from the phenol-like groups,but from the synergy between adjacent phenol-like groups,as well as the removal of unfavorable carbonyl groups on h-GQDs.In a mouse model of AKI,h-GQDs can effectively protect kidneys from oxidative injury and show no evidence of toxicity.3.Current diagnostic methods for sepsis are lack of required speed or precision,often failing to make timely accurate diagnosis for early medical treatment.The systemic excess generation of ROS during sepsis,has been considered as an early indicator of septic potential.Herein,we present the rational design of novel activatable nanoprobes(ROS CAs)composed of clinically-approved iron oxide core,Gd-DTPA,and hyaluronic acid(HA)that can image ROS via magnetic resonance imaging(MRI),and use them as sensitive contrast agents for sepsis evaluation.Such a well-defined nanostructure permits it to undergo a ROS-triggered degradation behavior and release Gd-DTPA in the presence of ROS,leading to the recovery of quenched T1-weighted MRI signal with fast response.With outstanding sensitivity and unlimited tissue penetration depth,ROS CAs are capable of imaging systemic ROS overproduction in mice with early sepsis.Moreover,by using these well-prepared ROS CAs,the severity of the sepsis can be rapidly evaluated by monitoring the systemic ROS levels in vivo.