Rgdf Peptide Modified Hydroxyethyl Starch Nanoparticles With Drug Load For Liver Cancer Chemotherapy

Liver cancer is one of the common malignant tumors.The main clinical treatment methods include surgical removal,radiation therapy,chemotherapy and immunotherapy.Chemotherapy is used in the early stage of liver cancer,which is also used in the preoperative or postoperative period and in the case of metastases frequently.Doxorubicin(DOX)is a commonly used drug for liver cancer chemotherapy.However,DOX is poorly soluble in water,and its toxicity also limit its clinical applications.Several natural polysaccharides have now been used as nanocarriers for different chemotherapeutic drugs.Polysaccharides have several advantages:(1)containing amino groups,hydroxyl and other reactive groups;(2)high hydrophilicity can help the drug to circulate in vivo for a longer period of time;(3)nanocarriers built by the modified polysaccharide have the ability to release the loaded drugs in a controlled manner.Hydroxyethyl starch is hydrophilic and has nanoparticle characteristics.Carboxylated hydroxyethyl starch is loaded with Adriamycin with opposite charge by adsorption to construct drug carrier.However,because hydrophilic groups are difficult to enter cells,so we plans to link RGDF peptide with active targeting function to modified hydroxyethyl starch.This paper mainly includes the following:(1)The carboxylated hydroxyethyl starch was synthesized by etherification of hydroxyl group of hydroxyethyl starch with chloroacetic acid under alkaline conditions,and the carboxyl group on carboxylated hydroxye thyl starch was activated by NHS/EDC catalytic system.The amino group on the RGDF peptide undergoes an amide reaction,which results in a certain dissociation of the carboxyl group in the water.The structures of intermediate products and target products were characterized by 1H-NMR and FT-IR.The results showed that RGDF peptide was successfully attached to hydroxyethyl starch chain.(2)The particle size distribution of the nanoparticles was investigated by dynamic light scattering technique.The morphology of the nanoparticles was further characterized by transmission electron microscopy(TEM).(3)By preparing and measuring the drug loading of the active targeted carboxylated hydroxyethyl starch-adriamycin system,a nano drug-loading system with a drug loading of 6% can be obtained,and the nano drug-loading system is investigated in the intracellular environment.(4)The in vitro antitumor activity of carboxylated hydroxyethyl starch-doxorubicin and active targeting carboxylated hydroxyethyl starc h-doxorubicin(RCHES@DOX)was studied by MTT.Compared with free doxorubicin,drug-loaded nanoparticles have a poor inhibitory effect on tumor cells at low concentrations.At high concentrations,the inhibition of tumor cells,especially RCHES@DOX,can almost achieve the same inhibitory effect as free doxorubicin.