The Design And Research Of Hollow S-nitrosothiols Nanoparticle For Nitric Oxide (NO)-releasing As Hepatic Tumor Targeted Chemotherapy

Background:Liver cancer,as a common malignant cancer,seriously endangers health.The main clinical treatments include surgical resection,interventional therapy,radiotherapy,and drug therapy.Surgery and radiotherapy have a good effect on some early patients.However,as the development course of the liver cancer is not easy to be detected,many patients missed the therapeutic window period.Furthermore,even after surgery,the recurrence possibility still exists,and the drug treatment is required.Compared with the characteristics of traditional drug therapy,precise targeted drug therapy with the application of nanotechnology has developed rapidly.After reasonable size control and structure design,the nano-drug systems show well drug delivery stability,biocompatibility,and targeted controlled release performance.Meanwhile,in the targeted therapy strategy,the researchers have been always focusing on designing "magic pill" for accurately identifying the pathological sites in the body,including various small molecular drugs and drug loading systems designed by the ligand-receptor or the physiological properties of the pathological sites.Although the target delivery systems have done a lot of works in the aspects of circulating time in vivo and drug leakage during transmission,these ectogenic drug delivery systems still need to be further studied and improved on(1)improving the efficacy of targeted therapy,and(2)reducing toxicity and side effects.Based on this,it will be a good strategy to find endogenous substances existing in the body as drugs.Nitric oxide(NO)palys messenger role to regulate many physiological functions in the body.Physiological concentration of NO regulates important physiological activities in cardiovascular,respiratory,nervous system,and immune response systems.When normal NO synthesis pathway in the body is problematic,it is necessary to provide NO-releasing materials as drug to meet the normal physiological needs.On the other hand,high concentrations of NO will form highly reactive substances(such as N2O3,ONOO-,etc.),resulting in nitrification and oxidative stress to excessive consume glutathione,block the normal function of mitochondria,destroy DNA,and induce cells apoptosis.In view of the important physiological function of NO and the difference of the effect of NO in the body caused by concentration change,it would be a good strategy to design and develop the NO-releasing materials as targeted therapy systems.Under this circumstance,the intelligent NO-releasing materials will recognize and identificate the target cells and tissues,release high concentration of nitric oxide stimulated by the specific physicochemical properties,resulting apoptosis of these cells and tissues.Futhermore,the small amount of inevitable NO leakage during the circulation process can participate in normal physiological activities without causing serious side effects.On the basis of literature reports,this paper intends to design and synthesize intelligent responsive NO-releasing nanoparticles for liver cancer tharget therapy systems.An intelligent responsive functional shell with multiple recognition mechanisms to liver tumor cells(or tissues)will be constructed on the surface of NO-loading nanoparticles.The functional shell,on the one hand,can protect the NO-loading inner layer of the nanoparticles during the circulation process in vivo to reach the target site successfully;on the other hand,also endows a good ability to recognize the target cells and tissues with sequent degradation around the physiological environment,triggering the NO-releasing in high concentration to play cell apoptosis mechanism.Meanwhile,the small amount of NO release during the internal circulation will participate in normal physiological activities without causing serious side effects,providing a new strategy for the fusion of "nitric oxide chemical biology" and "precise targeted therapy" of liver cancer.