A Targeted Mulifunctional Platform for Imaging and Treatment of Breast Cancer and Its Metastases Based on Adenoviral Vectors and Magnetic Nanoparticles
Final rept. 17 Jul 2006-16 Jun 2008
ALABAMA UNIV IN BIRMINGHAM
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Nanotechnology holds many promises for the imaging and treatment of breast cancer. In particular, magnetic nanoparticles can be utilized for tumor imaging via magnetic resonance imaging MRI techniques and tumor treatment by heating after exposure to an alternating magnetic field. However, selective targeting of the nanoparticles to the tumor cells needs to be accomplished before the imaging or therapy can be successful. In this respect, adenoviral Ad vectors for gene therapy have made great progress in achieving successful tumor targeting after their intravenous administration. We therefore hypothesized that coupling magnetic nanoparticles to targeted Ad vectors would allow the selective localization of these particles to the tumor, thereby making imaging and therapy possible. We herein identified that coupling gold nanoparticles to the Ad capsid protein hexon does not perturb vector infectivity or retargeting efficiency in vitro. Furthermore, we identified that available magnetic nanoparticles did not provide enough contrast to be suitable for Ad-mediated delivery and subsequent MRI. We therefore pursued the coupling of quantum dots QDs as an alternative imaging-method, and demonstrated that Ad vectors can deliver these intracellularly in breast cancer cells. However, QDs abrogated transgene expression of the Ad vectors by reasons not related to size or coupling chemistry. Future research will aim at identifying the reasons for transgene abrogation.
- Medicine and Medical Research