Aptamer train formed by hybridization and enzymatic ligation for specifically delivering MTZ to colon cancer cells

Multivalent interactions enhance targeted drug delivery by enabling stronger, specific binding to overexpressed receptors on target cells. This multivalent approach improves targeting efficiency, increases local drug concentration, and reduces off-target effects. This study explores the development and application of a multivalent species name as aptamer train (AT) composing of AS1411 aptamer and mitoxantrone (MTZ), an anticancer drug, for targeted therapy against colorectal cancer cells. The multivalent AS1411 aptamer with high specificity for nucleolin overexpressed in cancer cells, was synthesized using a hybridization and enzymatic ligation to enhance its stability and binding efficiency. MTZ was effectively intercalated into the AT, creating a multifunctional therapeutic system. The resultant nanostructure demonstrated strong and specific binding affinity to SW480 cells, as confirmed by fluorescence imaging and flow cytometry assays, indicating precise targeting capability. Furthermore, the MTZ-loaded AT exhibited significant cytotoxicity against SW480 cells while minimizing off-target effects on normal cells. These findings highlight the potential of the multivalent system as a novel targeted therapeutic approach for colorectal cancer, combining the specificity of the aptamer with the efficacy of the chemotherapeutic agent. It also serves as a platform for anti-cancer drug delivering to treat various types of cancer.