Soon-Jong Kim1 2, James Blumling III1, Marie C. Davidson3, Helen Saad1, Su-Yong Eun1 4, and Gabriel A. Silva1 3 ∗ † 1Department of Bioengineering, University of California, San Diego, CA, USA 2Department of Chemistry, Mokpo National University, Chonnam, Korea 3Department of Ophthalmology, University of California, San Diego, CA, USA 4Department of Physiology, College of Medicine, Jeju National University, Jeju, Korea
The application of nanotechnology to the field of medicine is now at the cutting edge of scientific research. Named as Nanomedicine, this smart strategy is aimed to find new approaches for therapeutic application in the difficult-to-treat pathologies, as neurological diseases. Applied to Central Nervous System (CNS) pathologies, nanocarriers, engineered for the specific passage across the Blood-Brain Barrier (BBB), have been widely studied with stimulating and interesting results. The in vivo and in vitro experiments clearly demonstrated the potential of this kind of approach, that, now, clearly needs a higher grade of translation of the research to preclinical model of pathologies. This paper provides for an incisive description of the rationale and the development of nanomedicine applied to neuroscience, the neuro-nanomedicine.
The delivery of drugs or genes to the inner ear in a controlled and biocompatible manner could lead to new treatments for conditions such as Meniere’s disease, tinnitus, schwannomas of the ear, and for improving hearing. The concept of multifunctional nanoparticles, which are targetable, biodegradable, and traceable, has led to new approaches to controlled drug release and localized delivery to specific cell populations. Tissue-specific delivery can be achieved by functionally “addressed” nanostructures loaded with a therapeutic molecule. In the present study, we investigated the incorporation, distribution, and toxicology of amphiphilic block copolymer nanoparticles (NPs) in spiral ganglion (SG) cell cultures. Adult human and guinea pig SG neurons and glia/Schwann dissociated cell cultures were expanded, grown for several weeks, and then studied live using time-lapse video microscopy and high-resolution light microscopy. The cells were further characterized using immunocytochemistry for the neural marker TuJ1 and the glia cell markers S-100 and GFAP, and their morphology was studied in more detail using scanning electron microscopy (SEM). These cell cultures were exposed to fluorescently (Dil)-loaded NPs for different time periods and at different concentrations, and the uptake was studied using fluorescence microscopy. The study demonstrates that DiI-loaded NPs can be internalized into guinea pig SG neurons as well as into human and guinea pig SG glia/Schwann cells without indication of toxicity or reduced viability. After 4 hours, almost 100% of both the neurons and the glia cells had incorporated the NPs into the cytoplasm. No uptake could be detected in the nucleus and no evidence of internalization could be seen in axons or in the growth cone area of the neuron. Especially in the glia cells, the NPs were detected in small vesicles surrounding the nucleus and occasionally in the periphery of the cytoplasm. This information could lead to the development of more specialized NPs, targeting only SG neurons or Schwann cells.
Microtubules are dysfunctional in a number of neurological and neuropsychiatric disorders, and there is evidence of their decreased stability. This article critically evaluates the feasibility of introducing microtubules with superior structural properties into dysfunctional brain areas to restore normal microtubule functions such as transport. Various approaches in biotechnology and nanotechnology exist that might be successful in this regard. One strategy is to design artificial tubulin genes, or DNA constructs, with specific point mutations that would subsequently (1) affect polymerization and depolymerization of microtubules, (2) alter posttranslational modifications, or (3) modify binding of microtubule-associated proteins—all in the direction of enhancing overall microtubule stability. Another strategy is to coat or functionalize the surface of microtubules, altering their properties in the direction of enhanced stability. The abnormal functioning of microtubules and their binding proteins is turning out to be a prominent defect found in separate neuronal populations of those diagnosed with Alzheimer’s disease, Parkinson’s disease, schizophrenia, or bipolar disorder. The current treatments for these disorders have met with varying degrees of success, and many of the treatments are associated with serious side effects. Nanotechnology and biotechnology can make significant contributions to the development of future treatments. DNA constructs for novel tubulins and nanoengineered “bionic” microtubules stand to vastly expand the biomedical arsenal of potential treatments aimed at repairing microtubules. Nonetheless, a great deal of research still needs to be done before such goals can be realized.
In recent years, the potential of nanowires for applications within nanomedicine, including drug delivery and diagnostics, have been explored by several groups. The small diameter of nanowires allows them to cross the lipid bilayer of the cell membrane without causing significant damage, which makes them attractive as a tool for gaining access to the intracellular environment. Recent studies report on an approach using vertically aligned nanowires fixed to a surface instead of nanowires in solution. Nanowire arrays hold promise of simpler maneuvering and additional applications within drug delivery, biosensing, and electrophysiology in living cells, all of which are explored in this paper.
