Metallated DNA Aptamers For Prostate Cancer Treatment
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2012
- Accession Number
- ADA559240
Entities
People
- William Gmeiner
Organizations
- Wake Forest University