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

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.