Preparation Of Arsenic-albumin Nanoparticles For Effective Cancer Therapy

Cancer has become the second cause of death over the world according to the report from World Health Organization?WHO?,and even worse,more and more young people tend to suffer from cancer disease.Present cancer treatment strategies mainly include chemotherapy,surgery,and radiotherapy,but these methods have their own limitations,leading to insufficient treatment efficacy.Chemotherapy as a regular cancer treatment can kill tumor cells effectively,but can also result in severe toxicity against normal cells at the same time.Therefore,it is highly interesting to develop new strategies for improving targeted delivery of cancer drugs and reducing its side toxicity.Nanomedicines have become a new choice of chemotherapy due to their tumor targeting ability and accumulation at tumor.Arsenic drug is an old drug found in traditional Chinese medicines such as arsenic trioxide and realgar,and now is usually used for the treatment of hematological malignant tumors.For example,arsenious acid injection is very effective in treating acute promyelocytic leukemia?APL?.The purpose of this project is to load arsenic drug into albumin nanoparticles for improving the tumor targeted delivery of arsenic drug and reducing its side-effect;moreover,the anticancer efficacy of arsenic-albumin nanoparticles is enhanced through combination chemotherapy and photothermal therapy.Purpose:Firstly,we will prepare arsenic manganese loaded albumin nanoparticles and characterize their physicochemical properties such as hydrodynamic size and size distribution,drug loading,TEM size.And then,we will investigate the drug release behaviors at pH 5.0 and pH 7.4.Furthermore,we will employ MTT to evaluate the cytotoxicity of arsenic manganese loaded albumin nanoparticles against cancer cells.Hopefully,we can achieve arsenic nanoparticles for thermo-chemotherapy with reduced side effect.Methods:Firstly,we incubated human serum albumin?HSA?with Mn²⁺ions to form complex of HSA-Mn,followed by adding arsenic sodium solution to produce insoluble arsenic manganese-HSA nanoparticles.The preparation of arsenic manganese-HSA nanoparticles was optimized by varying HSA concentration,molar ration of manganese chloride and arsenic sodium,pH values,temperature,and reaction time.The obtained nanoparticles were characterized using TEM observation,DLS,and ICP.The drug release of arsenic manganese-HSA nanoparticles studied at pH 5.4 and pH 7.4.Moreover,the cytotoxicity against cancer cells under irradiation or not was evaluated using MTT.The tumor-targeting ability of the established nanoparticles was studied by near-infrared fluorescence imaging in vivo.Results:The obtained arsenic manganese-HSA nanoparticles are well suspended in solution,showing spherical or sphere-like shape under TEM oberservation and hydrodynamic sizes of about 100 nm with a narrow size distribution.The drug loading of arsenic element in the nanoparticles is about 5.0%.The release of As and Mn species at pH5.4 is quicker than that at pH 7.4,indicating a preferred drug release after cellular uptake.Importantly,the arsenic manganese-HSA nanoparticles exhibited enhanced inhibition against A549 cells as compared to free arsenic sodium.