Nerve growth factor loaded macrophage-derived nanovesicles for inhibiting neuronal apoptosis after spinal cord injury

J Biomater Appl. 2021 Aug;36(2):276-288. doi: 10.1177/08853282211025912. Epub 2021 Jun 24.

Abstract

Spinal cord injury (SCI) is an extremely destructive central nervous system lesion. Studies have shown that NGF can promote nerve regeneration after SCI. However, it cannot produce the desired effect due to its stability in the body and is difficulty in passing through the blood-brain barrier. In this study, we prepared nanovesicles derived from macrophage membrane encapsulating NGF (NGF-NVs) as a drug carrier for the treatment of SCI. Cell experiments showed that NGF-NVs were effectively taken up by PC12 cells and inhibited neuronal apoptosis. In vivo imaging experiments, a large quantity of NGF was delivered to the injured site with the aid of the good targeting of NVs. In animal experiments, NGF-NVs improved the survival of neurons by significantly activating the PI3K/AKT signaling pathway and had good behavioral and histological recovery effects after SCI. Therefore, NVs are a potential drug delivery vector for SCI therapy.

Keywords: Spinal cord injury; macrophage membrane; nanovesicles; nerve growth factor; neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / metabolism
  • Biocompatible Materials / pharmacology
  • Cell Line
  • Cell Membrane / chemistry
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Macrophages / chemistry*
  • Macrophages / cytology
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanostructures / chemistry*
  • Nerve Growth Factor / chemistry*
  • Nerve Growth Factor / pharmacology
  • Nerve Growth Factor / therapeutic use
  • Neurons / cytology
  • Neurons / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Signal Transduction / drug effects
  • Spinal Cord Injuries / therapy
  • Tissue Distribution

Substances

  • Biocompatible Materials
  • Nerve Growth Factor
  • Proto-Oncogene Proteins c-akt