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

Biochem Biophys Res Commun. 2018 Feb 12;496(3):911-920. doi: 10.1016/j.bbrc.2018.01.123. Epub 2018 Jan 31.

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.

Keywords: BDNF; Cationic nanobubble; Gene therapy; LIFU; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Brain-Derived Neurotrophic Factor / administration & dosage*
  • Brain-Derived Neurotrophic Factor / genetics
  • Cations
  • Delayed-Action Preparations / administration & dosage*
  • Fluorocarbons / radiation effects
  • Gene Targeting / methods
  • Genetic Therapy / methods*
  • High-Energy Shock Waves
  • Male
  • Molecular Targeted Therapy / methods
  • Nanocapsules / chemistry
  • Nanocapsules / radiation effects*
  • Nanospheres / chemistry
  • Nanospheres / radiation effects
  • Rats
  • Rats, Sprague-Dawley
  • Sonication / methods*
  • Spinal Cord Injuries / genetics*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / therapy*
  • Treatment Outcome

Substances

  • Brain-Derived Neurotrophic Factor
  • Cations
  • Delayed-Action Preparations
  • Fluorocarbons
  • Nanocapsules
  • BDNF protein, human
  • perflutren