The time is right for the development and implementation of a powerful new
method to treat tinnitus. The necessity for this advancement centers on the observation
that over 50 million individuals are affected by this condition, ~3 million are seriously
disabled, effective treatments remain elusive, and there is no cure. To address this
formidable problem, we describe a theranostic nanoparticle-based drug-delivery
platform to localize and treat tinnitus by attenuating hyperactive neural activity in
regions of the brain affected by this condition. The driving force underlying this
approach centers on the multi-functionality of nanoparticles (NPs). Specifically, their
exterior surfaces can be decorated with multiple ligands designed to cross the bloodbrain-
barrier (BBB), target specific receptors in brain regions responsible for tinnitusrelated
hyperactivity, have the ability to encapsulate contrast agents so that tinnitusrelated
neural activity can be spatially localized in the brain using magnetic resonance
imaging (MRI), and have their central core loaded with a pharmacological agent,
enabling a payload of drugs to be delivered to those regions of the brain affected by
this condition. In theory, this approach will attenuate and/or eliminate tinnitus-related
hyperactivity; hence, markedly reduce or remove the tinnitus percept from
consciousness.
To date, an ex vivo model and in vivo animal experiments suggest that capsid-based
NPs are able to cross the BBB, which is an essential first step for this technology to
succeed. Optimization of NP concentrations, loading therapeutic and imaging agents,
and further exploring over expressed receptor targets for delivery to specific brain
regions are currently underway.
Keywords: Blood-Brain-Barrier, Drug Delivery, Functional Magnetic Resonance
Imaging, Low Density Lipoprotein Receptor, Magnetic Resonance Imaging, Manganese
Enhanced Magnetic Resonance Imaging, Molecular Imaging, Nanoparticle,
Nanotheranostics, Permanent Threshold Shift, Post-traumatic Stress Disorder, Receptor-
Mediated Transcytosis, Receptor Targeting, Temporary Threshold Shift, Tinnitus,
Traumatic-Brain Injury. Endothelial cells, Central nervous system, Functional magnetic
resonance imaging, Mangafodipir, Messenger ribonucleic acid, N-methyl-D-aspartate 2D
subunit, N-methyl-D-aspartate 2B subunit, Real-time polymerase chain reaction,
TeslaScan, Transwell permeable inserts.
