Fabrication of a nano polymer wrapping Meg3 ShRNA plasmid for the treatment of cerebral infarction

Artif Cells Nanomed Biotechnol. 2018;46(sup2):894-903. doi: 10.1080/21691401.2018.1471483. Epub 2018 Jun 29.

Abstract

Cerebral infarction is with poorer prognosis and high rates of mortality. After cerebral infarction, the promoting angiogenesis can accelerate the recovery of neurological function. Long non-coding RNA (LncRNA) maternally expressed gene 3 (Meg3) was overexpressed in cerebral infarction area and the knockdown of Meg3 promotes neovascularization and improves nerve function. In this study, we fabricated a nano-polymer wrapped Meg3 short hairpin RNA (ShRNA) plasmid to knockdown Meg3 and conjugated with OX26 antibody (MPO) to realize the brain targeting for the treatment of cerebral infarction. The MPO particle size was 103 ± 11 nm (PDI = 0.27) detected by dynamic light scattering (DLS) and the zeta potential of MPO was -32 mV. MPO achieved brain microvascular endothelial cell (BMEC) targeting and enhanced endothelial cells migration (p < .05), and tube formation (p < .05) in vitro. MPO realized brain tissue target, reduced the volume of cerebral infarction (p < .05) detected by TTC staining, increased capillary density through the HE staining and increased cerebral cortex micro-vessel through immunofluorescence method in vivo. The angiogenesis associated genes Vegfa, and Vegfr2 were upregulated after the treatment of MPO, compared with Meg3 or control plasmid treated group. This study suggested that MPO could achieve brain target and significantly promoted angiogenesis and became a new treatment method for cerebral infarction.

Keywords: Brain target; Cerebral infarction; Meg3; OX26.

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cerebral Infarction / genetics
  • Cerebral Infarction / physiopathology
  • Cerebral Infarction / therapy*
  • Drug Carriers / chemistry
  • Gene Knockdown Techniques
  • Male
  • Nanoparticles / chemistry*
  • Neovascularization, Physiologic / genetics
  • Plasmids / genetics*
  • Polyglutamic Acid / chemistry*
  • RNA, Long Noncoding / chemistry
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / genetics

Substances

  • Drug Carriers
  • MEG3 non-coding RNA, rat
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Polyglutamic Acid
  • Vascular Endothelial Growth Factor Receptor-2