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Contrast Ultrasound Targeted Treatment of Gliomas in Mice via Drug-Bearing Nanoparticle Delivery and Microvascular Ablation
Published on: December 15, 2010
Ultrasound-Mediated Targeted Delivery of ROS-Responsive Scavenging Nanomicelles for the Treatment of Ischemic Stroke
Xiangyi Zhou1,2, Zhengxin Wang1, Siying Li1
1Department of Ultrasound, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Purpose:
Ischemic stroke (IS) is a highly disabling and fatal cerebrovascular disease. Current vascular recanalization often triggers an explosive burst of reactive oxygen species (ROS) and a subsequent neuroinflammatory storm, leading to severe reperfusion injury. However, existing neuroprotective strategies face dual translational bottlenecks: the blood-brain barrier (BBB) restricts drug penetration, and conventional carriers cannot precisely modulate the deep ischemic microenvironment. To overcome these limitations, this study developed a dual-targeted delivery strategy combining low-intensity pulsed ultrasound with microbubbles (LIPUS-MBs) and ROS-responsive scavenging anti-inflammatory nanomicelles (TPLN).
Results:
The ROS-responsive scavenging TPLN nanomicelles were successfully synthesized. In vitro experiments demonstrated that TPLN efficiently scavenged intracellular ROS, protected PC12 neurons from oxygen-glucose deprivation (OGD)-induced apoptosis, and promoted the M2 repolarization of BV2 microglia. In vivo, the acoustic cavitation of LIPUS-MBs safely and reversibly permeabilized the BBB, increasing the targeted accumulation of TPLN within the ischemic lesion of MCAO rats. TPLN effectively mitigated oxidative damage and drove microglial polarization from a pro-inflammatory M1 state to a neuroreparative M2 phenotype, interrupting the oxidative stress-neuroinflammation cycle. Consequently, this synergistic therapy reduced cerebral infarct volume, alleviated brain edema, and facilitated neurological functional recovery.
Conclusion:
The dual-targeted delivery system combining LIPUS-MBs-mediated physical BBB opening and ROS-responsive scavenging TPLN chemical targeting provides a highly translatable therapeutic platform for the precision management of ischemic stroke. However, as these findings are primarily based on an acute-phase rodent model, the long-term therapeutic effects and clinical translational applicability require further investigation.
