Least component-based delivery of drug-tagged-nanocarriers across blood-brain-barriers (BBB) will allow site-specific and on-demand release of therapeutics to prevent CNS diseases. We developed a non-invasive magnetically guided delivery of magneto-electric nanocarriers (MENCs), ~20 nm, 10 mg/kg, across BBB in C57Bl/J mice. Delivered MENCs were uniformly distributed inside the brain, and were non-toxic to brain and other major organs, such as kidney, lung, liver, and spleen, and did not affect hepatic, kidney and neurobehavioral functioning.

Hydrogel-based drug delivery systems (DDSs) have versatile applications such, as tissue engineering, scaffolds, drug delivery, and regenerative medicines. The drawback of higher size and poor stability in such DDSs are being addressed by developing nano-sized hydrogel particles, known as nanogels, to achieve the desired biocompatibility and encapsulation efficiency for better efficacy than conventional bulk hydrogels. In this review, we describe advances in the development of nanogels and their promotion as nanocarriers to deliver therapeutic agents to the central nervous system (CNS). We also discuss the challenges, possible solutions, and future prospects for the use of nanogel-based DDSs for CNS therapies.

The negative factor (Nef) of human immunodeficiency virus (HIV) is an accessory protein that is thought to be integral to HIV-associated immune- and neuroimmune pathogenesis. Here, we show that nef-transfected microglia-released Nef+ exosome (exNef) disrupts the apical blood-brain barrier (BBB) and that only nef-transfected microglia release Nef in exosomes. nef-gfp-transduced neurons and astrocytes release exosomes but did not release exNef in the extracellular space. Apical administration of exNef derived from nef-transfected 293T cells reduced transendothelial electrical resistance (TEER) and increased permeability of the BBB. Microglia-derived exNef applied to either the apical/basal BBB significantly reduced expression of the tight junction protein, ZO-1, suggesting a mechanism of exNef-mediated neuropathogenesis. Microglia exposed to exNef release elevated levels of Toll-like receptor-induced cytokines and chemokines IL-12, IL-8, IL-6, RANTES, and IL-17A. Magnetic nanoparticle delivery of Nef peptides containing the Nef myrisolation site across an in vitro BBB ultimately reduced nef-transfected microglia release of Nef exosomes and prevented the loss of BBB integrity and permeability as measured by TEER and dextran-FITC transport studies, respectively. Overall, we show that exNef is released from nef-gfp-transfected microglia; exNef disrupts integrity and permeability, and tight junctions of the BBB, and induces microglial cytokine/chemokine secretion. These exNef-mediated effects were significantly restricted by Nef peptides. Taken together, this study provides preliminary evidence of the role of exNef in HIV neuroimmune pathogenesis and the feasibility of a nanomedicine-based therapeutics targeting exNef to treat HIV-associated neuropathogenesis.

Health agencies have declared the recent Zika-virus (ZIKV) infection an epidemic and a public health emergency of global concern due to its association with microcephaly and serious neurological disorders. The unavailability of effective drugs, vaccines, and diagnostic tools increases the demand for efficient analytical devices to detect ZIKV infection. However, high costs, longer diagnostic times, and stringent expertise requirements limit the utility of reverse transcriptase-polymerase chain reaction (RT-PCR) methods for rapid diagnostics. Therefore, developing portable, sensitive, selective, and cost-effective sensing systems to detect ZIKV at pM concentrations in biofluids would be a breakthrough in diagnostics and therapeutics. This review highlights the advancements in developing smart sensing strategies to monitor ZIKV progression, with rapid point-of-care (POC) diagnostics as the ultimate aim.

In this research, we demonstrate cell uptake of magneto-electric nanoparticles (MENPs) through nanoelectroporation (NEP) using alternating current (ac)-magnetic field stimulation. Uptake of MENPs was confirmed using focused-ion-beam assisted transmission electron microscopy (FIB-TEM) and validated by a numerical simulation model. The NEP was performed in microglial (MG) brain cells, which are highly sensitive for neuro-viral infection and were selected as target for nano-neuro-therapeutics. When the ac-magnetic field optimized (60 Oe at 1 kHz), MENPs were taken up by MG cells without affecting cell health (viability > 92%). FIB-TEM analysis of porated MG cells confirmed the non-agglomerated distribution of MENPs inside the cell and no loss of their elemental and crystalline characteristics. The presented NEP method can be adopted as a part of future nanotherapeutics and nanoneurosurgery strategies where a high uptake of a nanomedicine is required for effective and timely treatment of brain diseases.