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.
"Disruption of the blood-brain barrier using microbubble-mediated focused ultrasound" Taken from: https://fusfoundation.org/mechanisms-of-action/blood-brain-barrier-disruption Source: