Introduction Focused ultrasound FUS sonication in the presen
Focused ultrasound (FUS) sonication in the presence of microbubbles (MB) can disrupt the BBB, increasing its permeability. This type of disruption is transient and reversible, and does not damage neural cells. The oscillation and destruction of microbubbles as well as microstreaming and radiation forces are the key factors possible to create the transient rupture of vascular barriers and subsequent increase in the tumor\'s vascular permeability. This method could provide a means for targeted delivery of therapeutic or diagnostic agents to the brain.
Focused ultrasound with chemotherapeutic agent
Focused ultrasound with nanoparticles Advances in nanotechnology and molecular biology have allowed the development of novel nanomedical platforms. The superparamagnetic properties of magnetic nanoparticles (MNPs) allow them to be guided by an externally positioned magnet. However, their therapeutic use in treating CNS pathologies in vivo is limited by insufficient local accumulation and retention resulting from their inability to traverse the BBB. Therefore, combined use of focused ultrasound and magnetic targeting synergistically delivers therapeutic MNPs across the blood–brain barrier to enter the ampa both passively and actively. To test the effect of FUS-BBB opening for enhanced nanoparticles (for example: MNPs, approximate 200 nm) to penetrate to brain parenchyma, rat studies were performed. FUS treatment alone increased local deposition of MNPs relative to the contralateral hemisphere. Subsequently applying MT (application of magnetic field) caused the greatest increase in MNPs accumulation. Treatment experiments showed that combining magnetic nanoparticles with the FUS and magnetic guidance procedure provided the most effective means of controlling tumor progression. MRI monitoring of the tumor size demonstrated significant tumor growth repression; furthermore, the MNP accumulations were shown during pathology examination and transmission electron microscope imaging (Fig. 2).
Targeted drug delivery and nanoparticle-mediated hyperthermia therapy
From small to large animals Unlike a single element transducer with fixed focus at the geometric center, an ultrasound phased array can steer the focus of the ultrasonic energy to an arbitrary position by driving each element with a signal of the appropriate phase. We have designed a prototype of a 256-channel ultrasound phased-array system to perform localized BBB disruption, which demonstrates the feasibility of simultaneous, dual-frequency exposure from an ultrasound array. The large animal (swine) experiments confirmed the feasibility of inducing a large BBB-opened region by electronic scanning via phase switching control, and also demonstrated the potential to enhance the BBB-opening effect through dual-frequency FUS exposure.
Focused ultrasound with navigation Neuronavigation-guided FUS in the swine brain has the potential to become a flexible medical tool for drug delivery across the BBB into the human brain. The application of a neuronavigation system in guiding FUS for BBB opening will provide a new and more flexible route for accomplishing FUS-enhanced brain drug delivery and is expected to speed up the translation process and widespread use of this technology. The ultimate goal of this study is to develop an innovative nanodrug-chemotherapy and thermal therapy for tumor treatments using noninvasive focused ultrasound under neuronavigator-guidance and monitoring (Fig. 4, Fig. 5).
Conclusion and perspective
Conflict of interest
Introduction Adjuvant oral endocrine therapy (ET) demonstrates significant survival benefits in postmenopausal breast cancer patients with positive hormone receptor (HR). However, some of the patients taking either tamoxifen or aromatase inhibitor (AI) experienced ET-related adverse events. For tamoxifen, common adverse events include hot flash, endometrial thickening, vaginal spotting or thromboembolic events. For AI, arthralgia and loss of bone density may occur. These adverse events may affect patients\' adherence to a daily pill regimen, not to mention further medication intake for the next five years.