Improved outcome of targeted delivery of chemotherapy drugs to the brain using a combined strategy of ultrasound, magnetic targeting and drug-loaded nanoparticles

摘要

Ultrasound (US) application has been demonstrated to be capable of generating localized opening of the blood-brain barrier (BBB) and enhanced transport of therapeutic agents such as chemotherapeutic drugs and antibodies into the brain in animal models [1-11]. Liu et al. recently reported new results of a comprehensive study using a combined approach of US technique, magnetic targeting (MT), and drug-loaded magnetic nanoparticles (MNPs) to improve delivery of epirubincin (a chemotherapeutic drug used to treat malignant tumors) into a brain tumor in a rat model [12]. This is the fitst study to demonstrate the synergistic benefit of US-mediated BBB opening and additional mechanisms, and it illustrates a promising new venue for future development of US-mediated dtug delivery across the BBB to the brain. The synergistic delivery is achieved by using MNPs as a multifunctional agent for conjugating epi-rubicin, MT and MRI monitoring of delivery. MRI monitoring of US-induced BBB opening and MNP deposition in the brain was performed and corroborated with post-US assay results of MNP accumulation and epirubicin concentration in brain tissue. By comparing the delivery outcome (MNP accumulation and epirubincin concentration) in normal brain and tumor by US alone, MT alone and a combination of US plus MT, the authors clearly showed that the combination of US and MT achieved significantly increased delivery and therapeutic outcome in terms of tumor progression and animal survival.