Research Highlight


Dual targeting, pH sensitive surface switching mitochondrial specific nanoparticle drug delivery system. This system delivers a drug which inhibits mitochondrial function and induces apoptosis in cancer cells. The drug is delivered directly to the mitochondria by (1) targeting PSMA overexpression on prostate cancer tumor cells and (2) after cellular uptake, escaping from the endosome using a pH sensitive surface switching mechanism and targeting the mitochondria of the cancer cells. Source: BWH

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

An emerging method for targeting drugs to disease areas is to exploit the local changes that occur due to disease pathology and use these changes as triggers to improve targeting. This is accomplished by developing stimuli-responsive materials that change their physicochemical or drug-release properties upon encountering specific environmental cues, potentially leading to increased drug delivery to diseased tissues. These environmental cues may include low pH, inflammation, the presence of certain unique enzymes, and the reducing environment of endosomes. It may be possible to improve nanoparticle (NP) targeting to sites of disease by causing changes in NP surface properties at the target sites. In addition, the design of nanoparticles that can be internalized by endocytosis and thus release their active drugs inside subcellular organelles can be used to overcome multidrug resistance in cancer cells. In this project we develop surface switching NPs that can target first prostate cancer cells using a small molecule ligand and then the mitochondria specifically following endocytosis and endosomal release using a mitochondrial targeting peptide. This system would then be able to deliver its drug, which promotes pro-apoptosis signaling factors, directly to the mitochondria of the cell and create an efficient anti-cancer treatment.

 

 


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

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

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

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

Combined Cisplatin and Olaparib nanoparticles for ovarian cancer therapy

Co-delivery of protective substrate and chemotherapy drugs via lipid Bilayer Mesoporous Silica Nanoparticles

Digital diffraction diagnostics for lymphoma and HPV

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

Clinical immunotherapy application in metastatic glioblastoma

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

Longitudinal assessment of tumor heterogeneity during immunotherapy for metastatic melanoma

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

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

Optimization of macrophage-targeted nanoparticles for positron emission tomography imaging in cancer

Implementation of novel MR-based attenuation correction in PET/MR pelvic scans

Injectable thermogelling cisplatin-loaded hydrogels for combined chemo-radiation therapy in cervical cancer

Nanoencapsulation of tyrosine kinase inhibitors and their effects on pathway inhibition

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

Identification of novel therapeutic targets of the Notch1 signaling pathway

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

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

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

Online monitoring and image-guided treatment of chemoresistant micrometastases

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

Quantitative Multimodal Imaging of Tumor Response to Radiation


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