Study On The Synthesis Of A New Free Radical Inducer And Its Anti-tumor And Antibacterial Efficacy

Tumor drug resistance and antibiotic resistance are one of the most serious clinical problems,which have plagued the medical community for many years.Therefore,it is particularly important to find a treatment that is not easy to develop drug resistance.As a new type of treatment,free radical therapy uses oxidative damage to achieve therapeutic effects on tumor cells and pathogens,and it is not suitable to cause drug resistance,which has become a research hotspot in recent years.Regarding tumor free radical therapy,there are photodynamic therapy,chemical dynamic therapy and other treatment methods,but the above-mentioned treatment efficiency is severely limited by the level of free oxygen in the tumor tissue,because the tumor tissue is hypoxic,resulting in worrying treatment efficiency.For drug-resistant pathogens,finding new safe and effective free radical inducers is also the key to combating current clinical drug-resistant bacteria.Based on the above problems,this paper designs a new oxygenindependent nano-free radical inducer to improve the efficiency of tumor free radical therapy;and extracts and screens natural small molecule compounds from natural products for efficient free radical therapy of drug-resistant bacteria,The specific description is as follows:1.Copper Peroxide Nanoparticles(CP)Oxygen-independent Free Radical Production and Its Anti-tumor EffectsHere we construct a metal peroxide(MPs)composed of metal ions and peroxide groups.Among them,the metal Cu2+has excellent Fenton catalytic activity.Because the peroxide group can spontaneously and efficiently produce hydrogen peroxide under acidic conditions,it can make up for the shortage of H2O2 supply.We use a one-step reaction to synthesize copper peroxide(CP)nanodots.CP can provide Fenton-like Cu2+and H2O2 to enhance the generation of free radicals.With the assistance of hydroxide ions(OH-)and polyvinylpyrrolidone(PVP)as a stabilizer,CP nanodots were prepared by the reaction of H2O2 and Cu2+.The role of OH-is to deprotonate H2O2,thereby promoting the coordination of H2O2 and Cu2+,and anchoring the resulting waterinsoluble CP nanodots on the PVP surface to obtain a hydrodynamic diameter of about 16.3 nm PVP coated CP nano dots.Due to the small particle size of CP nanodots,the permeability and EPR effect of the tumor site can be fully utilized.More importantly,the CP nanodots treated with weak acid can quickly decompose into Cu2+and H2O2,and then a phenomenon similar to the Fenton reaction occurs.After breast cancer cells ingest CP nanodots,the pH-sensitive CP nanodots decompose in the acidic inner membrane of the lysosome,so that Cu2+catalyzes the Fenton reaction to release a large amount of H2O2,and then produces highly toxic·OH radicals,which are then passed Lipid peroxidation(LPO)process leads to the killing of tumor cells,and the inhibition rate of breast cancer cells is as high as 90%within 24 hours.All in all,the synthesized CP nanodots can provide H2O2 by themselves,overcoming the dependence on oxygen.In the weak acid environment of lysosomes,it causes lysosomal degradation,leading to tumor cell death,and has a good anti-tumor effect.2.Study on the antibacterial activity of triphenylsesquilignan analogues of star anise destroying biofilm through free radicalsStar anise(llicium simonsii Maxim)is an evergreen tree or shrub mainly distributed in India,Myanmar and southwestern China.Its roots,leaves,and fruits are often used as folk medicines for the treatment of cystic hernia,chest obstruction,qi pain,stomach cold and vomiting,etc.According to the recent research of the research group,the crude extract of I.simonsii showed antibacterial activity against MRSA.Based on this,we used fractional extraction to isolate 7 compounds,and determined their structures using nuclear magnetic resonance and mass spectrometry.And it was screened for its anti-Staphylococcus aureus activity,and it was found that compound 6 has the best antibacterial activity against Staphylococcus aureus(MIC=2μg/mL).Next,the mechanism of its antibacterial activity was studied.Through the destructive experiments of biofilms,it was found that the antibacterial effect of the production of free radicals leading to the oxidation and decomposition of biofilm lipids.In addition,by investigating its drug resistance,hemolysis characteristics and plasma stability in vivo,the results show that it is not easy to induce bacterial resistance,and it has low hemolytic activity and good plasma stability.The above experimental results show that compound 6 has the ability to induce free radicals to produce higher antibacterial activity and better in vivo safety,which provides a new experimental basis for the treatment of pathogenic bacteria and drug-resistant bacteria.