Abstract
AbstractAll chemotherapeutic treatments worldwide (>50%) use platinum‐based compounds. Despite their clinical success, an increasing number of platinum drug‐resistant tumors are reported, limiting the therapeutic application of these compounds. While various kinds of strategies are pursued to circumvent resistances, there remains a lack of understanding of how cancer cells develop platinum drug resistances. Within this study, the involvement of the DNA repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1) in the occurrence of platinum drug resistance is directly visualized in living cells by a DNA tetrahedron‐based molecular probe. Capitalizing on this biochemical insight, the suppression of the expression of APE1 in cancer cells is realized using a DNA tetrahedron‐based RNA interference technique, presenting a novel strategy to overcome platinum drug resistance. This study presents the first example of Pt(IV) complex loaded tumor aptamer‐modified DNA tetrahedrons with an APE1 specific small interfering RNA (siRNA) strand for suppression of APE1 expression and therapeutic treatment of patient‐derived platinum drug‐resistant lung cancer tumors.
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