Research Highlight


A) NIRF images showing the accumulation of the MN-EPPT probe in colon tumors. The tumor on the left lacks the uMUC-1 antigen (uMUC-1 -), while the tumor on the right does have the uMUC-1 antigen (uMUC-1 +). Signal from the probe is much higher in the uMUC-1 + tumor, as demonstrated by the center and right images showing raw fluorescence and a color coded map, respectively. B) NIRF images of excised tumor C) Fluorescence microscopy of the probe in excised tissue. Images demonstrate that the nanoprobe retained its structural integrity.

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

Early diagnosis and efficient treatment of tumors are essential to the survival of cancer patients. New molecular based therapies are beginning to allow treatment regimens that take advantage of a tumor's unique molecular characteristics. However, there is a need for more sophisticated imaging techniques to enable the effective application of these therapies. Imaging probes that are able to target tumors would help to facilitate earlier diagnoses, monitor tumor response to existing therapies, and facilitate the development of novel therapeutics. One class of probe currently being studied and refined are cross-linked, iron oxide nanoparticles carrying EPPT peptides. This molecule is a targeted, multi-modal imaging probe referred to as MN-EPPT. The EPPT peptide attached to the nanoparticle’s dextran coat is able to bind to the underglycosylated mucin-1 antigen, (uMUC-1) which is specifically expressed on the surface of human adenocarcinomas. As a result, the probe is able to accumulate selectively in tumor cells. uMUC-1 is present on almost 50% of all human cancers, including breast, prostate, lung, and pancreatic cancers, among others. The nanoparticles are designed for use with two different, yet complementary imaging modalities. The iron oxide is superparamagnetic, which means it is viable as a contrast agent for MR imaging. Furthermore, MN-EPPT particles are coated with a Cy5.5 dye, which allows them to be used for optical near-infrared imaging (NIRF). This dual functionality lets the probe take advantage of the unique benefits of each type of imaging. MRI provides high spatial and temporal resolution, and NIRF is known for its sensitivity. In addition, the presence of Cy5.5 dye allows for correlative fluorescence microscopy of excised tissues. The current project will evaluate MN-EPPT’s utility as a device for assessing tumor response to a standard chemotherapeutic, Gemcitabine, in a preclinical model of orthotopic pancreatic adenocarcinoma. This study will also validate the work done in previous projects that demonstrated MN-EPPT’s ability to accumulate selectively at the site of the tumor. Both MR and NIRF imaging will be used to examine the probe's feasibility as a tool for tracking changes in tumor size. In addition, we will investigate whether Gemcitabine causes downregulation of uMUC1 antigen during treatment, which may affect MN-EPPT’s ability to accumulate in tumor cells. This will be done by investigating uMUC1 mRNA expression and correlating it with MN-EPPT accumulation in tumors.

 

 


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:

Erythropoietin improves antitumor immune response through reversal of the hypoxic tumor microenvironment

MCT1 Transporter Inhibition of IMR90 Cells Expressing Inducible Merkel Cell Carcinoma Small T Antigen

Optimizing murine cells for in vitro modeling of high-grade serous ovarian cancer

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

Identifying genomic and compound dependencies in undifferentiated sarcomas

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

Targeting CXCR4/SDF-1a using phytochemicals to inhibit progression and metastasis of pancreatic cancer

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

miRNA analysis of up regulated miRNA-645 and miRNA-1290 in mouse orthotropic 4t1 model of metastatic breast cancer

Assessing the reproducibility of MRI-based brain tumor measurements between both observers and MRI vendors

Localized chemo- and chemo-radiation for the treatment of prostate cancer

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

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

Clinical immunotherapy application in metastatic glioblastoma

Digital diffraction diagnostics for lymphoma and HPV

Mechanistic and modeling studies of lipid nanoemulsions impact on oral lapatinib absorption

Targeting WASp using Wiskostatin-gold nanoparticles

Capture of circulating tumor DNA through the use of biotinylated poly-lysine affixed to gold nanoparticles

Biological mechanisms of gold nanoparticle-enhanced radiation therapy of prostate cancer

Software with built-in neuroanatomy atlas provides insight into cancer treatment

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

Quantitative Multimodal Imaging of Tumor Response to Radiation

Nanoencapsulation of tyrosine kinase inhibitors and their effects on pathway inhibition

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

Investigating the use of iron chelator deferoxamine (DFO)-bearing PEG-like nanoprobes as a multifunctional agent for cancer therapy and PET imaging


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