Research Highlight


Figure 1. (Top) Confocal microscopy image of PC3 cancer cells. Red indicates 30nm silica nanoparticles (SiNPs) with Cy5 dye encapsulated. Blue indicates stain for nucleic acids. Source: Unpublished original research, Jodi Belz and Noelle Castilla Ojo, Sridhar Laboratory, Northeastern University. Figure 2. (Bottom) (a) Illustration of intradermal spacer diffusion. As the spacer degrades, fluorescent silica nanoparticles are released for a slow sustained diffusion. Further, drug encapsulated in the nanoparticle can be released. A TEM image of (b) 30 nm and (c) 200 nm silica nanoparticles. (d) A series of SEM images of a flash frozen and fractured spacer with uniform distribution of nanoparticles. As magnification of the cross sectional area is enhanced, silica pockets are observed. Source: Nanomedicine Science and Technology Center, Sridhar Laboratory, Northeastern University.

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

Prostate cancer is the second leading cause of cancer-related deaths in men. While 5-year survival rates are high, prostate cancer is slow-growing and recurring tumors are often unresponsive to treatment. Salvage brachytherapy offers a second chance for cure but leads to high rates of rectal toxicity. The Sridhar lab, in collaboration with radiation oncologists at Dana Farber Cancer Institute, aims to locally radiosensitize the prostate throughout the duration of brachytherapy treatment to enable the use of lower radiation doses with lower toxicities for a greater chance of cure. Currently, brachytherapy uses inert spacers for spatial guidance during the one-time injection of radioactive seeds. We leverage the use of these spacers to create a new modality of chemo-radiation therapy, replacing the spacers routinely used in brachytherapy with our own biodegradable spacers doped with radiosensitizing drug Docetaxel, both with and without silica nanoparticles. Here the silica nanoparticles would allow for a highly controlled dual release platform in which first the nanoparticle is released from the spacer and second the drug is released from the nanoparticle. This approach provides localized in-situ delivery of the chemotherapeutic sensitizer directly to the tumor with enhanced uptake and avoids the toxicity associated with current systemic delivery. Complete understanding and characterization of the release kinetics of both the spacer and nanoparticle is crucial in developing an effective slow-sustained release of local chemotherapy with minimal adverse toxicities. These biodegradable implants have a robust platform and can incorporate a variety of different chemotherapeutics, nanoparticles, or biologics as a local delivery modality for varying diseases. As part of the CaNCURE project, we will continue to complete in vitro studies needed to understand the underlying properties and release of the spacer, the therapeutic efficacy of nanoparticles versus free chemotherapeutics, and the cellular uptake of the drug and particles. We will also continue to monitor the therapeutic impact in vivo of Docetaxel loaded spacers in PC3 xenografted mice. A full toxicity study will be completed to ensure the safety of the new device in comparison to currently used taxotere, in hopes of developing a safe and translatable new modality of chemotherapy.

 

 


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:

Combined Cisplatin and Olaparib nanoparticles for ovarian cancer therapy

Digital diffraction diagnostics for lymphoma and HPV

Quantification of SPION accumulation in tumors using positive-contrast MRI

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

Clinical immunotherapy application in metastatic glioblastoma

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

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

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

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

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

Development of PSMA-targeting nanoparticles for positron emitting tomography imaging in prostate cancer using animal models

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

Radiation enhancement in cancer cells using gold and gadolinium nanoparticles

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

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

Nanoencapsulation of tyrosine kinase inhibitors and their effects on pathway inhibition

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

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

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

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

Identification of novel therapeutic targets of the Notch1 signaling pathway

Targeting WASp using Wiskostatin-gold nanoparticles

Quantitative Multimodal Imaging of Tumor Response to Radiation

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

Identifying genomic and compound dependencies in undifferentiated sarcomas


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