Research Highlight

Inhibiting DNA repair after nanoparticle-amplified radiation therapy

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.



Trainee Research

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:

Tracking pancreatic adenocarcinoma response to treatment using targeted, multi-modal nanoparticles

Development of Smart INCeRT Brachytherapy Spacers via PLGA and Docetaxel for Combined Chemo-Radiation Therapies in Prostate Cancer

Investigation of a miRNA associated with cancer metastasis. Proj 2-Development of a novel nanoparticle for MPI analysis of thromboses

Delivery of Titanium Dioxide Nanoparticles via Biodegradable PLGA Dissolving Microneedles for Sustainable Release

Iron-chelating PEG-like nanoprobes as therapeutic and 89Zr/PET imaging agents

Small T Antigen Effect on Mitotic Proteins B-Myb and FOXM1

miRNA analysis in mouse model of metastatic breast cancer. (Proj 2) The inhibition of PD-L1 on a Pan02 cell line w/ siRNA-nanodrug & gemcitabine treatment

Longitudinal assessment of tumor heterogeneity during immunotherapy for metastatic melanoma

Uptake and localization of nanoparticles in prostate and lung cancer cells as a function of time and nanoparticle type

Protein-encapsulated nanoparticles for oral delivery of anti-mitotic agents in prostate cancer

Surface-targeting, ligand-switching nanoparticles for mitochondrial drug delivery in prostate cancer

Use of CT Texture Analysis for Characterization and Prognostication of Incidental Adnexal Lesions

Pharmacokinetic analysis of changes in temozolomide distribution after antiangiogenic treatment of glioblastoma

Quantification of SPION accumulation in tumors using positive-contrast MRI

Digital diffraction diagnostics for lymphoma and HPV

Use of a Triblock Copolymer Hydrogel for Controlled Release of Cisplatin and BMN-673

Investigating the use of Feraheme to monitor the immune response by PET in general inflammation and specific immune cell populations

Development of a novel nanogel for non-invasive transdermal delivery of cancer vaccines using hyaluronic acid

Discovering the Genetic Mechanism of Enhanced Metastatic Colonization in SMAD4 Mutant Tumors

Quantitative Multimodal Imaging of Tumor Response to Radiation

Development of a Point of Care Assay for Detecting High Risk HPV in Resource Limited Settings

Combined Cisplatin and Olaparib nanoparticles for ovarian cancer therapy

T1-weighted imaging of primary pancreatic adenocarcinoma using magnetic ferumoxytol nanoparticles

Clinical immunotherapy application in metastatic glioblastoma

Radiotherapeutic synergism of thermogelling cisplatin-loaded polymers for cervical cancer treatment

Soleil Doggett (Biology, '16) talks to her fellow peers about her research on oxygenating tumors to stimulate the anti-tumor immune response.


Trainee e-portfolios

Photo credit: Tom Kates Photography

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.

Check out this month’s featured e-portfolios by Rachel Fontana and Jordan Harris!


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