Design And Preparation Of Lysosome Biodegradable Platinum Drug Conjugates

Malignant tumor is one of the threats to human health, which leads to high incidence and fatality rate. Chemotherapy drugs are applied to treat quite a few of cancers, which make good effects. Based on high cytotoxicity, platinum drugs are widely used. The application of platinum drugs is limited to its side effects and drug resistances. Improvements of structure have been realized in order to overcome these defects. Meanwhile, new types of drug deliveries are used to deliver platinum drugs to the tumor with increasing stability in blood circulation. In addition, prodrug binding with targeted moleculars is able to enhance its specificity.New kinds of bivalent platinum drugs are prepared in this paper, which is based on cisplatin and dichlorodiaminocyclohexaneplatinum. The methods of structural characterizations are IR,1H NMR and MS, which proves that target products have been obtained.Val-Cit based linker is also synthesized in this paper, which is lysosome biodegradable. The prodrugs are prepared that bind linker to synthesized bivalent platinum drugs. Intermediates and target compounds are determined by IR, 1H NMR, 13C NMR, and MS.BSA coupled platinum prodrugs are prepared, which is simulate targeted molecular drug conjugates. The molecular ratios of these conjugates are 5.42 and 5.23 respectively. Cumulative drug release rates are 68.23% and 67.94% respectively, which are determined after 45 hours in the condition of cell disruption solutions. Moreover, the cumulative drug release rates are 27.43%、 27.21% in the condition of pH 7.2, which are measured after 60 hours. Cell survival rates of conjugates are higher than cisplatin under the same drug concentrations. In other words, cell proliferation inhibition effect of conjugates is poor to cisplatin. Cell survival rates of conjugates are more than 50% when drug concentrations of Pt reach 50μM.