Biochemical and Biophysical Research Communications, Vol.496, No.3, 911-920, 2018
Noninvasive, targeted gene therapy for acute spinal cord injury using LIFU-mediated BDNF-loaded cationic nanobubble destruction
Various gene delivery systems have been widely studied for the acute spinal cord injury (SCI) treatment. In the present study, a novel type of brain-derived neurotrophic factor (BDNF)-loaded cationic nano bubbles (CNBs) conjugated with MAP-2 antibody (mAb(MAO-2)/BSNF/CNBs) was prepared to provide low intensity focused ultrasound (LIFU)-targeted gene therapy. In vitro experiments, the ultrasound -targeted tranfection to BDNF overexpressioin in neurons and efficiently inhibition neuronal apoptosis have been demonstrated, and the elaborately designed mAb(MAO-2)/BSNF/CNBs can specifically target to the neurons. Furthermore, in a acute SCI rat model, LIFU-mediated mAb(MAO-2)/BSNF/CNBs transfection significantly increased BDNF expression, attenuated histological injury, decreased neurons loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in SCI rats. LIFU-mediated mAb(MAO-2)/BSNF/CNBs destruction significantly increase transfection efficiency of BDNF gene both in vitro and in vivo, and has a significant neuroprotective effect on the injured spinal cord. Therefore, the combination of LIFU irradiation and gene therapy through mAb(MAO-2)/BSNF/CNBs can be considered as a novel non-invasive and targeted treatment for gene therapy of SCI. 2018 Elsevier Inc. All rights reserved.