The Construction Of Noble Metal Nanozymes And Its Application In Tumor Treatment

Due to the complicated growth and metabolism mechanism of tumor cell,long latency period and escape immune system recognition,tumor treatment has become a difficult problem for researchers.In addition,the morbidity and mortality of tumor have been high and even increased year by year.At present,there are a variety of tumor treatment methods,changing with each passing day,but a single treatment method is far from enough to cure tumor.In response to this dilemma,researchers have proposed the combination therapy strategy,which has brought about a promising way of cure tumors.Combination therapy aims to achieve the therapeutic effect of"1+1>2" by integrating multiple treatment methods.However,the complex operation process and multiple administration toxicity limit the practical application of combination therapy.Therefore,the "integration" of various therapeutic methods is an effective strategy to overcome these difficulties.In addition,tumor microenvironment is obviously different from normal tissue,and it is a hot topic in the field of tumor therapy to utilize the characteristics of tumor microenvironment to realize or enhance tumor treatment effect.Noble metal nanozymes are favored by researchers because of its catalytic performance that similar to natural enzyme and high stability.Based on the catalytic activity of noble metal nanozymes and endogenous substances of tumor,they designed a series of cascade catalytic reactions to disrupt tumor microenvironmental homeostasis and lead to tumor cell death.In conclusion,based on the enzyme activity of nanozymes,it is feasible to design a multifunctional treatment platform of noble metal nanozymes enhanced by enzyme catalysis for enhancing the effect of tumor combination therapy and reducing side effects.In this paper,PdPtCu nanozymes with multi-enzyme activity and PtBi nanozymes with single-enzyme activity were designed and synthesized,and a multifunctional nano-therapy platform was constructed based on their enzyme activity,and its therapeutic effect was studied for tumor cells.The main contents are described as follows:(1)PdPtCu nanozymes with multi-enzyme activity was synthesized by hydrothermal reactor,and then PdPtCu nanozymes was etched with hydrochloric acid to form a porous structure.Etched PdPtCu nanozymes loaded immune checkpoint inhibitor-Indoleamine-(2,3)-dioxygenase inhibitor(NLG919)and subsequently modified with bovine serum albumin(BSA)to improve its water solubility.Multifunctional nanocomposites(PdPtCu/NLG919@BSA-Ce6/ER)was prepared by connecting amino groups on proteins with photosensitizer Ce6 and ER targeting molecule.PdPtCu nanozymes have catalase,peroxidase and glutathione(GSH)peroxidase activities.On the one hand,PdPtCu nanozymes could produce O2 to alleviate hypoxic and enhance photodynamic therapy;on the other hand,it consumed GSH and produced-OH for chemodynamic therapy.Then,under 1064 nm irradiation,PdPtCu nanozymes have good photothermal effect.Therefore,ER guided nanoparticles to the endoplasmic reticulum of tumor cells,and the synergistic effects of chemodynamic therapy,photodynamic therapy and photothermal therapy could cause strong endoplasmic reticulum stress and stimulate tumor immune response.At the same time,NLG919 blocked the immune escape of tumors and enabled them to be recognized by T cells,thus achieving the goal of multimodal treatment of tumor.(2)PtBi noble metal nanozymes with single catalase activity and photothermal properties were prepared by a simple one-pot hydrothermal method.PtBi-DSPE-PEG nanoplatform was constructed by amphipathic micelle DSPE-PEG modification.Then,the modification of Ce6 or GOx on the surface of it was explored,indicating that Nanocomposites based on PtBi have the potential to construct combination therapy system.In addition,the small molecule drug NLG919 loaded by Nanocomposites was studied,indicating that Nanocomposites based on PtBi can be used for small molecule drug delivery research.Cell experiments showed that PtBi-DSPE-PEG nanocomposites had good CAT-like activity and photothermal therapeutic effect.The nanocomposites are expected to be further functionalized for the study of the"integration" of various therapy.