Grant: Operating Grant: SickKids-CIHR-IHDCYH New Investigator Grants

<html> <head> </head> <body> <span align="start" style="letter-spacing: normal; text-indent: 0px; text-transform: none; white-space: normal; word-spacing: 0px; display: inline !important; float: none"><font color="rgb(0, 0, 0)" face="Times New Roman" size="medium">Use of medications during pregnancy is extremely common and incurs significant risks to the developing fetus. Among pregnancy-associated diseases, breast cancer is an escalating clinical problem but it lacks an effective cure. Chemotherapy can treat the mother but incurs significant risks to the fetus and the pregnant woman. We propose to develop a novel therapy that will exclusively targets the maternal tumor during early pregnancy. We will design new techniques to evaluate the therapeutic efficacy and safety of this new therapy. These techniques override conventional models that fail to mimic the dynamic physiological environment of human pregnancy and the tumor microenvironment. Specifically, we will design tumor-targeted doxorubicin-loaded nanoparticles (NPs) using the technology of microfluidics (manipulation of fluids in microscale channels). We will be the first to use novel integrated dynamic organ-on-a-chip models, developed in our lab, to recapitulate both the placental barrier and the tumor microenvironment of a pregnant woman with cancer. We will use this technology to test the ability of these NPs to target the tumor cells and their potential fetal and maternal risks. Potential NP candidates will be further evaluated for biodistribution, fetal and maternal safety and efficacy using pregnant mice with breast tumor xenografts. The project is innovative in three key areas. (1) The interaction between cancer and pregnancy to develop targeted tumor therapies has not been previously considered. (2) Prenatal nanomedicine is in its infancy. (3) Our approach is both innovative and translational because it uses integrated organ-on-a-chip technology to develop foundational knowledge about NP outcomes under dynamic conditions recapitulating human pregnancy and tumor microenvironment. This project will lay the groundwork for safe and efficacious therapies for pregnancy-associated breast cancer&#8212;a challenging clinical condition that currently lacks any efficient treatment option. This will be a significant breakthrough for maternal and fetal health.</font></span> </body> </html>