Reactive Oxygen Species-Mediated Pd-Based Nanozymes-Combined Photothermal And Chemodynamic Therapies

Reactive oxygen species(ROS)are byproducts of aerobic respiration in living organisms,including oxygen ions,peroxides,and oxygen radicals,etc.Among them,hydroxyl radical(·OH)and superoxide anion(·O2-)are highly reactive,which can peroxidize biomacromolecules(lipids,proteins,and nucleic acids),hence inhibiting or eradicating pathogenic bacteria and tumor cells.Many strategies have been devised in purpose of bolstering ROS yields,in which nanozyme stands out for a few advantages.A nanozyme can mimic the catalytic mechanism of one or more natural enzymes to catalyze rapid generation of abundant ROS from oxygenated substrates;besides,the facile preparation,high stability during physiological treatments,and adjustable enzyme-like activities,altogether,have given rise to the widespread presence of nanozymes in studies of biomedicine.Herein the study was constructed in the aim of amplifying ROS signals at the focus of disease.For that purpose,we developed therapeutic platforms based on two-dimensional(2D)palladium nanozymes.We clarified the mechanism of in situ ROS generation catalyzed by and the regulatory effect on redox equilibrium of living cells by palladium-based nanozymes.Aligned with near-infrared Ⅰ region(NIR-Ⅰ)photothermal therapy or chemodynamic therapy,our therapeutic nanoplatforms realized successful antibacteria and antitumor effects,respectively,at bacterial and cellular levels.Accordingly,the efficacy and safety of the photoenhanced antibacteria therapy and the chemodynamic/nanozyme therapy were evaluated at animal level,respectively.Followings are brief introductions to each of the chapters:Chapter 1:We summarized the definition,origin,and categorization of ROS,as well as its regulatory effect on life cycles,particularly the dual sides of ROS.First,the therapeutic characteristcs of ROS were elaborated in terms of two fields,antitumor and antibacteria.Next,a selection of nanozymes was introduced in details,including their categorization and functionalities;correspondingly,related published works were epitomized regarding their synthesis and preparation,cancer therapy,and infection therapy.Then,various therapeutic models mediated by ROS and novel therapies developed from these models in collaboration with various nanozymes were presented,followed by leading examples of research achievements.Lastly,the topic and contents of our works were proposed.Chapter 2:In this chapter,we devised and synthesized Pd-PEG nanozyme,characterized its physical and chemical properties,evaluated its peroxidase(POD)-like activity and photothermal conversion capacity,verified the synergistic effect between photothermal effect and enzyme-like activity.At bacterial level,we thoroughly investigated the bactericidal and biofilm eradicating effect of Pd-PEG nanozyme.Besides,we clarified the antibacterial mechnism of Pd-PEG.Finally,we applied our photoenhanced synergistic antibacteria platform on live animals,and efficiently relieved the infection and accelerated the wound healing process.Chapter 3:In this chapter,we devised PPA nanogenerator,a chemo drug artesunate(ART)-loaded nanozyme based on Pd@Pt nanoplate.We characterized PPA’s physical and chemical properties,POD-like activity,controlled drug release behavior,and the ability of amplifying ROS signals via dual pathways.We not only explored the PPA-elevated intracellular oxidative stress and the subsequent cellular damage,but also demonstrated at animal level the high accumulation of PPA at tumor sites.As a result,we successfully proved the antitumor efficacy of our nanozyme/chemodynamic therapeutic platform.Chapter 4:In this chapter,we made the overall conclusion of our current works and rational outlook into future research.