Monitoring of ultrasound targeted drug delivery with liquid biopsy

The characterization of brain cancer genetic and molecular characteristics along with monitoring their response to therapeutic interventions is critical for effective treatment. Liquid biopsy—a minimally invasive technique that uses cancer soluble markers, such as cell-free DNA, in blood samples—offers a unique method to characterize the molecular profile of brain tumors and monitor the response treatment, as their location limits the effectiveness of traditional methods, such as needle biopsy. However, due to the limited secretion of cancer soluble molecules from the tumor core and the bloodstream, presumably due to the presence of the blood–brain barrier (BBB), liquid biopsy suffers from low sensitivity. Here, we show that microbubble enhanced focused ultrasound (MB-FUS) can significantly enhance the secretion of macromolecules from the tumor core to the blood. We also observed that MB-FUS in combination with liquid biopsy can be used to assess chemotherapy effect on cell death type in brain tumors. Together our findings highlight the potential of liquid biopsy in combination with MB-FUS to overcome challenges associated with the limited secretion of cancer soluble molecules in the circulation and support its application for monitoring targeted drug delivery in brain tumors.