Noninvasive, targeted gene therapy for acute spinal cord injury using LIFU-mediated BDNF-loaded cationic nanobubble destruction.

Abstract:

: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 nanobubbles (CNBs) conjugated with MAP-2 antibody (mAbMAP-2/BDNF/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 mAbMAP-2/BDNF/CNBs can specifically target to the neurons. Furthermore, in a acute SCI rat model, LIFU-mediated mAbMAP-2/BDNF/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 mAbMAP-2/BDNF/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 mAbMAP-2/BDNF/CNBs can be considered as a novel non-invasive and targeted treatment for gene therapy of SCI.

authors

Song Z,Ye Y,Zhang Z,Shen J,Hu Z,Wang Z,Zheng J

doi

10.1016/j.bbrc.2018.01.123

subject

Has Abstract

pub_date

2018-02-12 00:00:00

pages

911-920

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(18)30138-4

journal_volume

496

pub_type

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