Metallated DNA Aptamers for Prostate Cancer Treatment

Abstract

The purpose of this project is to develop DNA aptamer complexes that are selectively cytotoxic to PSMA+ prostate cancer (PCa) cells. Our studies showed Zn2+ is cytotoxic to prostate cancer cells and also sensitizes PCa cells to chemotherapy. We developed a new DNA motif for Zn2+ delivery. We also developed a new chemical strategy for delivering the cytotoxic drug doxorubicin to cancer cells. We have demonstrated that our novel dimeric aptamer complexes are selectively internalized by PSMA+ prostate cancer cells and have demonstrated selective cytotoxicity with delivery of doxorubicin. We also developed a new nanoparticle (NP) composed of porphyrin and DNA and demonstrated that this NP was cytotoxic to bladder cancer cells in vitro, was non-toxic in vivo, and displayed strong anti-tumor activity in vivo. The aptamer complexes and the NPs we developed in this project are highly selective and highly active agents that have the potential to markedly improve chemotherapy for treatment of advanced prostate cancer.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2013
Accession Number
ADA578778

Entities

People

  • William H. Gmeiner

Organizations

  • Wake Forest University

Tags

DTIC Thesaurus Topics

  • Antineoplastic Agents
  • Bladder Cancer
  • Cancer
  • Cell Membrane
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Chemotherapy
  • Confocal Microscopy
  • Culture Techniques
  • Mass Spectrometry
  • Materials Science
  • Molecular Dynamics
  • Nanoparticles
  • Neoplasms
  • Organic Chemistry
  • Spectroscopy

Fields of Study

  • Chemistry
  • Medicine

Readers

  • Molecular Genetics
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech