Electro-Magnetic Nano-Particle Bound Beclin1 siRNA Crosses the Blood-Brain Barrier to Attenuate the Inflammatory Effects of HIV-1 Infection in Vitro

J Neuroimmune Pharmacol. 2017 Mar;12(1):120-132. doi: 10.1007/s11481-016-9688-3. Epub 2016 Jun 10.


The purpose of this study was to evaluate a novel drug delivery system comprised of ferric-cobalt electro-magnetic nano-material (CoFe2O4@ BaTiO3; MENP) bound to siRNA targeting Beclin1 (MENP-siBeclin1) to cross the blood-brain barrier (BBB) and attenuate the neurotoxic effects of HIV-1 infection in the central nervous system following on-demand release of siRNA using an in vitro primary human BBB model. Beclin1 is a key protein in the regulation of the autophagy pathway and we have recently demonstrated the importance of Beclin1 in regulating viral replication and viral-induced inflammation in HIV-1-infected microglia. The MENP-siBeclin1 nano-formulation did not compromise the physiological function or integrity of the BBB model. Furthermore, the in vitro BBB data revealed that MENP-siBeclin1 could efficiently attenuate viral replication and viral-induced inflammation, likely due to STAT1/ NF-κB signaling pathways. MENP-siBeclin1 also silenced Beclin1 protein expression in HIV-1-infected microglial cells within the model system. In addition, the cytotoxic effects of direct treatment with siBeclin1 and MENP alone or in nano-formulation on primary human neuronal cells showed a minimal amount of cell death. Overall, the data shows that the nano-formulation can silence the BECN1 gene as an effective mechanism to attenuate HIV-1 replication and viral-induced inflammation in the context of the BBB.

Keywords: Autophagy; Blood–brain barrier; HIV-1; Magneto-electric nano-particles; Neuro-inflammation; RNA interference.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Beclin-1 / administration & dosage
  • Beclin-1 / genetics
  • Beclin-1 / metabolism*
  • Blood-Brain Barrier / metabolism*
  • Cells, Cultured
  • Electromagnetic Phenomena
  • HIV Infections / genetics
  • HIV Infections / metabolism*
  • HIV Infections / prevention & control
  • HIV-1*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Inflammation / metabolism
  • Metal Nanoparticles* / administration & dosage
  • Microglia / drug effects
  • Microglia / metabolism
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*


  • Beclin-1
  • RNA, Small Interfering