纳米酶在疾病治疗中的研究与应用

Research and Application of Nanozymes in Disease Treatment

纳米酶是一种新型的具有类酶活性的纳米颗粒人工酶,在生物检测、抗炎、抗氧化损伤和癌症治疗等疾病诊断和治疗领域展现出良好的应用前景。本文总结了具有不同类酶活性的纳米酶在疾病诊治中的应用,并对影响纳米酶活性的主要影响因素进行了阐述,将使相关研究人员更好地了解纳米酶的发展现状,并提供后续研究的相关线索。

Nanozyme is novel nanoparticle with enzyme-like activity,which can be classified into peroxidaselike nanozyme,catalase-like nanozyme,superoxide dismutase-like nanozyme,oxidase-like nanozyme and hydrolase-like nanozyme according to the type of reaction they catalyze.Since researchers first discovered Fe3O4 nanoparticles with peroxidase-like activity in 2007,a variety of nanoparticles have been successively found to have catalytic activity and applied in bioassays,inflammation control,antioxidant damage and tumor therapy,playing a key role in disease diagnosis and treatment.We summarize the use of nanozymes with different classes of enzymatic activity in the diagnosis and treatment of diseases and describe the main factors influencing nanozyme activity.A Mn-based peroxidase-like nanozyme that induces the reduction of glutathione in tumors to produce glutathione disulfide and Mn2+,which induces the production of reative oxygen species(ROS)in tumor cells by breaking down H2O2 in physiological media through Fenton-like action,thereby inhibiting tumor cell growth.To address the limitation of tumor tissue hypoxia during photodynamic tumor therapy,the effect of photodynamic therapy is significantly enhanced by using hydrogen peroxide nanozymes to catalyze the production of oxygen from H2O2.In pathological states,where excess superoxide radicals are produced in the body,superoxide dismutase-like nanozymes are able to selectively regulate intracellular ROS levels,thereby protecting normal cells and slowing down the degradation of cellular function.Based on this principle,an engineered nanosponge has been designed to rapidly scavenge free radicals and deliver oxygen in time to save nerve cells before thrombolysis.Starvation therapy,in which glucose oxidase catalyzes the hydrolysis of glucose to gluconic acid and hydrogen peroxide in cancer cells with the involvement of oxygen,attenuates glycolysis and the production of intermediate metabolites such as nucleotides,lipids and amino acids,was used to synthesize an oxidase-like nanozyme that achieved effective inhibition of tumor growth.Furthermore,by fine-tuning the Lewis acidity of the metal cluster to improve the intrinsic activity of the hydrolase nanozyme and providing a shortened ligand length to increase the density of its active site,a hydrolase-like nanozyme was successfully synthesized that is capable of cleaving phosphate bonds,amide bonds,glycosidic bonds and even biofilms with high efficiency in hydrolyzing the substrate.All these effects depend on the size,morphology,composition,surface modification and environmental media of the nanozyme,which are important aspects to consider in order to improve the catalytic efficiency of the nanozyme and have important implications for the development of nanozyme.Although some progress has been made in the research of nanozymes in disease treatment and diagnosis,there are still some problems,for example,the catalytic rate of nanozymes is still difficult to reach the level of natural enzymes in vivo,and the toxic effects of some heavy metal nanozymes material itself.Therefore,the construction of nanozyme systems with multiple functions,good biocompatibility and high targeting efficiency,and their largescale application in diagnosis and treatment is still an urgent problem to be solved.(1)To improve the selectivity and specificity of nanozymes.By using antibody coupling,the nanoparticles are able to specifically bind to antigens that are overexpressed in certain cancer cells.It also significantly improves cellular internalization through antigen-mediated endocytosis and enhances the enrichment of nanozymes in target tissues,thereby improving targeting during tumor therapy.Some exogenous stimuli such as laser and ultrasound are used as triggers to control the activation of nanozymes and achieve specific activation of nanozyme.(2)To explore more practical and safer nanozymes and their catalytic mechanisms:biocompatible,clinically proven material molecules can be used for the synthesis of nanoparticles.(3)To solve the problem of its standardization and promote the large-scale clinical application of nanozymes in biomonitoring.Thus,it can go out of the laboratory and face the market to serve human health in more fields,which is one of the future trends of nanozyme development.