Defining Delivery Pathways of Nanoparticles | Wilson Poon, University of Toronto |PhD Defense

When:
February 13, 2020 @ 1:00 pm – 4:00 pm
2020-02-13T13:00:00-05:00
2020-02-13T16:00:00-05:00
Where:
Medical Sciences Building Room MSB3153
1 King's College Circle
M5S 1A8

Speaker: Wilson Poon

Institution: University of Toronto

Abstract: 

The goal of nanomedicine is to use nanoparticles to carry drugs to specific target site in the body. For
cancer nanomedicine, a recent meta-analysis showed that only 0.7% of the injected nanoparticles reach
the tumour. To address this delivery inefficiency, it is important to examine each biological barrier to
determine its impact on delivery. In this thesis, first the body was modelled as a series of barriers that
nanoparticles need to overcome successively in order to access the target site. The model shows that
the number and strength of barriers limits what is available to be delivered. The macrophages of the
liver can sequester up to 99% of the injected nanoparticles, and thus are the biggest barrier for targeted
delivery. Next, clodronate-liposomes were used to remove the liver macrophages and showed that both
nanoparticle tumour delivery and hepatobiliary elimination can be improved. Specifically, nanoparticle
tumour delivery can be increased up to 50× and hepatobiliary elimination up to 10×. Removal of the
liver macrophages then allowed the exploration of other secondary barriers to delivery such as tumour
pathophysiology and the liver sinusoidal endothelium. Together, these studies define concepts and
strategies that can improve nanoparticle delivery and reduce unwanted bioaccumulation to pave the
way for their clinical translation and regulatory approval.