Preparation of AS1411 Aptamer-Modified PEGylated Liposomal Doxorubicin and Evaluation of Its Anti-Cancer Effects in Vitro and in Vivo

Active targeting of the tumor microenvironment could be a helpful strategy to reduce toxicity and drug resistance. Encapsulating anticancer agents in liposomes has improved tumor accumulation and decreased nonspecific toxicity. In this study, the potential of nucleolin-targeted PEGylated liposomal doxorubicin (PLD) to convey doxorubicin into tumor was compared to PLD. The effect of liposome coupled AS1411 aptamer (AS-PLD) was assessed via cytotoxicity, competition assay, and cellular uptake in vitro. Additionally, liposome biodistribution and pharmacokinetic analysis as well as its therapeutic efficacy were assessed in mice C26 tumor models. The cytotoxicity and cellular uptake results demonstrated that AS-PLD is more potent than PLD in killing cancer cells. The competition assay indicated the specificity of the AS-PLD in targeting C26 cells in vitro. There was more AS-PLD accumulation in the tumor after 72 h post-injection. The present study demonstrated the more therapeutic efficiency of the AS-PLD compared to PLD, making this formulation a proper active-targeted formulation for cancer treatment.