Research Highlight


Nanoliposomes will be used to co-deliver a Tdp1-inhibiting antibiotic (tetracycline) and a topoisomerase inhibitor (camptothecin) to cancer cells, enhancing cell death with less systematic toxicity.

Co-delivery of antibiotics and topoisomerase inhibitors to overcome chemoresistance

In patients with recurrent platinum-resistant epithelial ovarian cancer, topoisomerase inhibitors (TPIs) are the most active second-line chemoagents; however, treatment response is underwhelming due to both drug resistance and systemic toxicity of TPIs. Topoisomerases are enzymes that cleave DNA strands to mediate relaxation of supercoiled DNA, allowing for the continuation of DNA replication and transcription. TPIs disrupt this process by trapping topoisomerase-DNA cleavage complexes, increasing the rate of topoisomerase-crosslinked DNA strand breaks. Tdp1 is an emerging therapeutic target that repairs the topoisomerase-DNA adduct by cleaving the 3’(5’)-tyrosyl-DNA bond between topoisomerase and DNA in cells, reducing the efficacy of the TPI. This function of Tdp1 makes it a potential therapeutic target that may be incorporated into treatment. Nanotechnology is used in this study to assist in targeting these enzymes by repurposing Tdp-1-inhibiting antibiotics in a mechanistically interactive combination with TPIs to provide a more effective treatment. The underlying hypothesis is that the ability of tetracycline antibiotics to reduce DNA repair inhibition of Tdp1 removes a barrier that mitigates camptothecin action. This combination, unbalancing the rate of DNA cleavage and religation, is anticipated to enhance cancer cell death. Co-encapsulation and co-delivery of the agents at high payloads in nanoliposomes will also aid in reducing systemic toxicity.The goal of the study will be achieved in two aims under the mentorship of Dr. Tayyaba Hasan (PI) and postdoctoral fellows (Drs. Huang and Obaid): Aim 1 (1-4 months) will synthesize and characterize multi-compartmental nanoliposomes to co-delivery tetracycline (antibiotic) and camptothecin (TPI). Aim 2 (4-6 months) will evaluate the combination treatment response in monolayer cultures of OVCAR-5-cisR (cisplatin-resistant ovarian cancer cell line derived from solid tumor).

 

 


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:

Co-delivery of antibiotics and topoisomerase inhibitors to overcome chemoresistance

The Assessment and Comparison of Ferumoxtran as Contrast Imaging Agent in Patients with Pancreatic Cancers.

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

Longitudinal assessment of tumor heterogeneity during immunotherapy for metastatic melanoma

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

Nanomedicine for Safe Healing of Bone Trauma

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

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

PDT and PIT with Chemotherapy for Treatment of 3D Ovarian Cancer Nodules Under Flow and Static Conditions

Assessment of Atherosclerotic Changes using Ferumoxytol as MRI Contrast Agent

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

Analysis of DREAM and E2F1 Competition for Cell Cycle Promoters during G1.

In vivo imaging of targeted drug delivery to HER2 positive cancer cells

Online monitoring and image-guided treatment of chemoresistant micrometastases

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

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

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

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

Quantification of SPION accumulation in tumors using positive-contrast MRI

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

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

Digital diffraction diagnostics for lymphoma and HPV

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

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

Nano-plasmonic exosome (nPLEX) assays for exosome analysis and antibody validation


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