The Molecular and Cellular Mechanisms for Nanoparticle Transport

The goal of cancer nanomedicine is to deliver drugs to the tumour using nanoparticles. However, this tumour delivery is not an efficient process. Less than 1% of nanoparticles injected into the blood will reach the tumour while the rest of nanoparticles accumulate in off-target tissues. To improve tumour delivery, it is crucial that we understand the delivery journey of nanoparticles. This PhD thesis contributes to this goal by identifying the major molecular interactions and cellular processes that determine nanoparticle distribution in the body. We discovered that cells use the LDL receptor to bind the apolipoprotein B and complement C8 proteins adsorbed on the nanoparticle surface to take up nanoparticles. Expression in the LDL receptor correlated with and thus predicted the amount of nanoparticle accumulation in mice organs. We also found that tumour endothelial cells predominantly use macropinocytosis to transport nanoparticles into the tumour. Macropinocytosis membrane ruffling is upregulated in the tumour endothelium compared to normal endothelium in healthy tissues, which might explain the elevated nanoparticle accumulation in the tumour. Overall, this thesis provides molecular information on the mechanisms of nanoparticle distribution in the body. Our findings could inform the creation of nanomedicine that blocks unwanted interactions while targeting useful tumour entry pathways. Enhanced delivery of drug-carrying nanoparticles will achieve better clinical outcomes for cancer patients.

Department dc:contributor.department

Biomedical Engineering

Year dc:date.issued

2024

Author dc:creator

• Wu, Liu Yi

Advisor dc:contributor.advisor

• Chan, Warren C. W.

Handle dc:identifier.uri

https://hdl.handle.net/1807/149707

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/149707