Validation of Novel Strategy in Treatment Delivery & Anti-Tumour Effects in Glioblastoma
Standing
Undergraduate
Type of Proposal
Oral Research Presentation
Challenges Theme
Open Challenge
Faculty Sponsor
Dr. Lisa Porter
Proposal
Glioblastoma (GBM) is the most common and aggressive brain tumor which continues to puzzle researchers as decades of efforts to find an effective therapy has proven to fail. Collaborative studies resulted in generation of particles of a microscopic size, known as conjugated polymer nanoparticles(CPNs). CPNs can serve as a potential therapeutic approach to overcome treatment barriers in GBM, which include drug penetration to the brain and presence of aggressive and resistant Tumour Initiating Cells (TICs). Our CPNs are labeled with Hyaluronic acid (HA-CPNs) which is a ligand for CD44, one of the most prominent receptors found on TICs. Results to date, have showed successful targeting of the CD44+ tumor cells followed by decrease of their proliferation in a dish as well as a decrease of tumor size grown in zebrafish models. To build on this data, my project will explore the application of HA-CPNs in delivery of GBM standard of care Temozolomide (TMZ) using TMZ labeled HA-CPNs (HAT-CPNs). We hypothesize that including TMZ molecules in the existing HA-CPN design will enhance the previously demonstrated effects of CPNs on human GBM. First, I will investigate the effects of HAT-CPNs on various GBM cell lines. I will measure the uptake of the particles by the glioblastoma cells, the particle cytotoxicity, and aggressive characteristics of TICs, including proliferation and their ability to from tumours in zebrafish, upon exposure to HAT-CPNs versus control. I will then investigate the molecular mechanisms underlying HA-CPN and HAT-CPN effects on CD44+ TIC populations. Careful validation of this advanced HA-CPN system will contribute to better understanding of the technology to improve its applications moving forward and towards better therapies for GBM patients in future.
Grand Challenges
Viable, Healthy and Safe Communities
Validation of Novel Strategy in Treatment Delivery & Anti-Tumour Effects in Glioblastoma
Glioblastoma (GBM) is the most common and aggressive brain tumor which continues to puzzle researchers as decades of efforts to find an effective therapy has proven to fail. Collaborative studies resulted in generation of particles of a microscopic size, known as conjugated polymer nanoparticles(CPNs). CPNs can serve as a potential therapeutic approach to overcome treatment barriers in GBM, which include drug penetration to the brain and presence of aggressive and resistant Tumour Initiating Cells (TICs). Our CPNs are labeled with Hyaluronic acid (HA-CPNs) which is a ligand for CD44, one of the most prominent receptors found on TICs. Results to date, have showed successful targeting of the CD44+ tumor cells followed by decrease of their proliferation in a dish as well as a decrease of tumor size grown in zebrafish models. To build on this data, my project will explore the application of HA-CPNs in delivery of GBM standard of care Temozolomide (TMZ) using TMZ labeled HA-CPNs (HAT-CPNs). We hypothesize that including TMZ molecules in the existing HA-CPN design will enhance the previously demonstrated effects of CPNs on human GBM. First, I will investigate the effects of HAT-CPNs on various GBM cell lines. I will measure the uptake of the particles by the glioblastoma cells, the particle cytotoxicity, and aggressive characteristics of TICs, including proliferation and their ability to from tumours in zebrafish, upon exposure to HAT-CPNs versus control. I will then investigate the molecular mechanisms underlying HA-CPN and HAT-CPN effects on CD44+ TIC populations. Careful validation of this advanced HA-CPN system will contribute to better understanding of the technology to improve its applications moving forward and towards better therapies for GBM patients in future.