The effect of AS1411 aptamer on anti-tumor effects of dendrimers containing SN38

Abstract

ObjectiveAlthough 7-Ethyl-10-hydroxy-camptothecin (SN38) is the most physiologically active of the camptothecin, its application has been limited due to its poor solubility in pharmaceutical solvents. Irinotecan is a prodrug of SN38 and the only commercially available formulation of this group. However, due to individual differences, the metabolism rate of Irinotecan to SN38 varies from person to person. In this study, we investigated the effect of aptamer functionalization on therapeutic efficiency of PAMAM dendrimers containing SN38. Methods and materialsAS1411 aptamer conjugated PEGylated PAMAM containing SN38 was prepared and characterized for drug loading and PEGylation efficiency. In vitro cytotoxicity and cellular uptake of SN38 in prepared formulations after 3 h of exposure to murine colon carcinoma (C26) cell line were investigated. Then in vivo anti-tumor efficacy and survival analysis were studied in C26 mice bearing tumor for 54 days. ResultsIn vitro evaluations revealed significantly higher cytotoxicity and much lower IC50 for all preparations compared to SN38 solution. Cellular uptake studies showed a higher value of uptake for aptamer conjugated formulations after 3 h of exposure. Regarding in vivo results, all prepared formulations improved survival of animal model. All PEGylated formulations conjugated with aptamer in dose of 1 mg/kg and 2 mg/kg and formulation conjugated with aptamer in dose of 2 mg/kg indicated significantly better tumor growth inhibition compared to Irinotecan (25 mg/kg). ConclusionThe results of this study showed that encapsulation of SN38 in dendrimer and modification of dendrimer by A1411 aptamer improved the anti-tumor effect of drug.