Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 33, Issue 2, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202208797
Keywords
APE1; DNA nanostructures; patient-derived xenografts; platinum drugs; siRNAs
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This study visualizes the involvement of the DNA repair enzyme APE1 in platinum drug resistance in living cells using a DNA tetrahedron-based molecular probe. It also demonstrates the suppression of APE1 expression in cancer cells using a DNA tetrahedron-based RNA interference technique, presenting a novel strategy to overcome platinum drug resistance.
All 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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