Enhanced delivery of camptothecin and doxorubicin conjugates with hyaluronic acid for the treatment of Glioblastoma using microbubble-mediated focused ultrasound
Mentor: Nathan McDannold, PhD (Brigham and Women's Hospital)
Glioblastoma (GBM) is the most common malignant brain tumor and carries notoriously poor prognosis. Current GBM chemotherapies are challenged by severe drug delivery obstacle due to the existence of the blood-brain barrier (BBB), which limits most drugs from gaining access to the brain. Previously we reported synergistic anti-tumor activities of camptothecin (CPT) and doxorubicin (DOX), and their conjugates with hyaluronic acid (HA) for treating breast cancer models. Here, we combine the use of HA-CPT-DOX conjugates and microbubble-mediated focused ultrasound (FUS) for treating GBM in mice. HA was selected as the carrier because of its biocompatibility and the targeting specificity for the surface marker CD44, which is over-expressed on many cancer cells. Spatially targeted transcranial FUS can open the BBB temporarily and enhance the delivery of the drug conjugates to the tumor targets inside the brain.
Endothelial cells that form the blood-brain barrier (BBB) have tight junctions, preventing most drugs in the blood stream from permeating the brain. Focused ultrasound reversibly opens the BBB by opening the these tight junctions, allowing most drugs into the brain. With the use of microbubbles, focused ultrasound further opens the BBB in a reversible manner to allow larger molecules, such as nanoparticles, into the brain. Source: https://fusfoundation.org/mechanisms-of-action/blood-brain-barrier-disruption Source: