More than 50% of cancer patients receive radiation therapy at some point during their care. Previous and ongoing studies have demonstrated that metallic nanoparticles like gold nanoparticles, can amplify the radiation dose by facilitating the ejection of low-energy (short range) photoelectrons. This radiation enhancement leads to increased DNA double strand breaks (DSBs) in nearby cells. When molecular targeting methods are employed, the increased DNA damage can be confined to specific subpopulations (e.g. cancer cells, tumor vasculature, etc.). Single strand breaks (SSBs) are normally repaired by base excision repair (BER). Poly ADP ribose polymerase (PARP) is a key component of BER and PARP inhibition leads, therefore, to persistence of SSBs. A replication fork may encounter a persistent SSB during DNA replication, which causes the replication fork to collapse or the formation of a double strand break. Previous studies have shown that agents such as PARP inhibitors (PARPi) can inhibit and prevent the repair of DNA double strand breaks caused by radiation damage. By inhibiting DSB repair, PARPi can amplify the effects of radiation therapy. My project will explore a strategy to combine the radiosensitizing ability of gold nanoparticles (AuNPs) in synergy with the DNA-repair inhibiting ability of PARPi. The hypothesis is that combining these treatments will lead to a greater therapeutic effect than each alone. To test this hypothesis, I will a) synthesize a liposomal formulation encapsulating functionalized gold nanoparticles in the aqueous core and PARPi in the lipid bilayer of the liposomes (Figure 1), b) characterize and test their in vitro efficacy in non-small cell lung cancer (NSCLC) cell line Calu 6, and c) evaluate the in vivo benefit of combined PARP inhibition and nanoparticle-amplified radiation therapy in mouse models of lung cancer. Standard assays to evaluate the cytotoxity (MTT), cell proliferation (clonogenic survival) and DNA double strand break (gamma-H2aX staining) will be carried out.
CaNCURE provides trainees with a 6-month hands-on research experience and one-on-one mentoring by leading researchers in cancer nanomedicine. Projects performed by current and past participants include:
While on co-op, trainees document their research in an e-portfolio. This gives trainees the opportunity to provide regular updates on their research progress, reflect on training they are receiving, and explain how their research fits within the field of cancer nanomedicine. These research e-portfolios can be accessed through individual trainee profiles. The complete collection may be found here.
Presentation at CaNCURE Nanomedicine Day
At the completion of their co-op, trainees are provided with the opportunity to present their research to a wider audience. In our 1st annual CaNCURE Nanomedicine Day, trainees prepared interactive, digital posters to display on electronic poster boards. Over 100 faculty, students, and researchers attended our first event!
Check out the news article and congrats to all the poster winners!
Jordan Harris: Most Innovative Cancer Research Award
Jeremy Thong: Best Undergraduate Research Poster Award
Craig Pille: Most Promising Translational Research Award
Bryan Kynnap: Most Promising Basic Science Award
Jordan Harris: Top Chemical Engineering Poster Award