关键词：脱氧核糖核酸；体内分析；前列腺癌；锌细胞；医药
摘 要：The purpose of this project is to develop aptamer-targeted DNA:Zn2+ complexes that are highly efficacious for prostate cancer treatment. Significant progress has been made on refining novel Zn2+-binding DNA motifs that utilize FdU nucleotides and that are highly cytotoxic towards prostate cancer cells. We demonstrated netropsin binding to the 3 -FdU DNA hairpin, clarified the mode of Zn2+ binding to this complex and demonstrated the Zn2+/DNA/netropsin ternary complex is highly cytotoxic towards prostate cancer cells. We also demonstrated DNA hairpins with stems consisting of G-FdU base pairs form complexes with Zn2+ that have increased stability at physiological pH relative to stems consisting of A-FdU base pairs. We completed SELEX and identified a new DNA aptamer to PSMA and demonstrated selective binding towards PSMA+ prostate cancer cells. We demonstrated that Zn2+-pyrithione is synergistic with FdUMP 10 for inducing cytotoxicity towards prostate cancer cells. We have purchased animals and are ready to evaluate Zn2+- pyrithione/FdUMP 10 in vivo in the coming months. All components are in place for forming the dimeric aptamer complexes and evaluating cytotoxicity in vitro and in vivo.