Non-invasive focused ultrasound-based synergistic treatment of brain tumors

Among the primary brain tumors, gliomas are the most commonly found. In the United States, these tumors account for approximately 78% of the new cases of primary malignant brain and central nervous system (CNS) tumors diagnosed annually. Glioblastoma multiforme (GBM) is the most common and aggressive type of glioma, with the poorest survival duration. Although surgical techniques, radiotherapy and chemotherapy have improved, the prognoses of patients with glioblastomas are still poor (∼1 year), which is largely because of the spread of tumor cells to other regions of the brain. Intravenous administration of chemotherapy drugs is the standard procedure for treat these spreaded cells, but the treatment effect is limited because of the adverse side effect and the delivery blockage from the blood–brain barrier (BBB). Thus, developing an effective treatment system to conquer this blockage will be beneficial for those who suffer from malignant brain tumor.Focused ultrasound (FUS) sonication in the presence of microbubbles (MB) may be able to promote the effectiveness of drug delivery, and help to overcome the blockage. The oscillation and destruction of microbubbles as well as microstreaming and radiation forces are the key factors capable of creating the transient rupture of the vascular barriers and subsequent increase in the tumor's vascular permeability.The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs, or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.