TMARC Pilot Studies - Active

Developing Nanotechnology for Therapeutic Targeting in NeuroHIV and Substance Abuse (Landon)

Agency: TMARC
PI: Landon, Preston, Ph.D.

Abstract

This proposal will apply a new form of nanotechnology, magnetic nanobowls (MNBs), to the problem of persistent reservoirs of HIV infection despite antiretroviral therapy (ART).  Such reservoirs are believed to be especially intractable in the brains of persons who abuse drugs such as methamphetamine (METH).  The brain presents significant challenges for delivery of therapeutics and diagnostics. MNBs represent the next generation of nanotechnology, designed to address these challenges. In addition to their magnetic capabilities, which provide for external control, they feature a customizable surface coat that directs the MNBs to a specific target location or cell type in the body. MNBs can be engineered to carry a payload, such as a therapeutic drug or diagnostic tag, that can be released under the control of an external radiofrequency field, or in an automated manner when the MNBs encounter a specific molecule in the body. In the current application, we will engineer MNBs, specifically for the brain).  The brain MNBs will have surface molecules (brain derived neurotrophic factor (BDNF), a ligand for trKB receptors) designed to target specific neuronal pathways of relevance to substance abuse. In Aim 2, we will use fluorescence microscopy evaluate neuro uptake of the MNB’s. In Aim 3 we will focus on obtaining preliminary data for future NIDA applications. We collect evidence on the brain MNBs using assays of oxidative stress and neuroinflammation to determine whether brain MNBs protect the neurons from METH-induced injury in vitro, as assessed by markers of neuronal damage and glial activation.

Sponsored by NIH/NIDA P50DA026306

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