Nanoneuroscience

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Nanoneuroscience is an interdisciplinary field that integrates nanotechnology and neuroscience. [1] One of its main goals is to gain a detailed understanding of how the nervous system operates and, thus, how neurons organize themselves in the brain. Consequently, creating drugs and devices that are able to cross the blood brain barrier (BBB) are essential to allow for detailed imaging and diagnoses. The blood brain barrier functions as a highly specialized semipermeable membrane surrounding the brain, preventing harmful molecules that may be dissolved in the circulation blood from entering the central nervous system.

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The main two hurdles for drug-delivering molecules to access the brain are size (must have a molecular weight < 400 Da) and lipid solubility. [2] Physicians hope to circumvent difficulties in accessing the central nervous system through viral gene therapy. This often involves direct injection into the patient’s brain or cerebral spinal fluid. The drawback of this therapy is that it is invasive and carries a high risk factor due to the necessity of surgery for the treatment to be administered. Because of this, only 3.6% of clinical trials in this field have progressed to stage III since the concept of gene therapy was developed in the 1980s. [3]

Another proposed way to cross the BBB is through temporary intentional disruption of the barrier. This method was first inspired by certain pathological conditions that were discovered to break down this barrier by themselves, such as Alzheimer’s disease, Parkinson’s disease, stroke, and seizure conditions. [2]

Nanoparticles

Nanoparticles are unique from macromolecules because their surface properties are dependent on their size, allowing for strategic manipulation of these properties (or, “programming”) by scientists that would not be possible otherwise. Likewise, nanoparticle shape can also be varied to give a different set of characteristics based on the surface area to volume ratio of the particle. [4]

Nanoparticles have promising therapeutic effects when treating neurodegenerative diseases. Oxygen reactive polymer (ORP) is a nano-platform programmed to react with oxygen and has been shown to detect and reduce the presence of reactive oxygen species (ROS) formed immediately after traumatic brain injuries. [5] Nanoparticles have also been employed as a “neuroprotective” measure, as is the case with Alzheimer’s disease and stroke models. Alzheimer’s disease results in toxic aggregates of the amyloid beta protein formed in the brain. In one study, gold nanoparticles were programmed to attach themselves to these aggregates and were successful in breaking them up. [6] Likewise, with ischemic stroke models, cells in the affected region of the brain undergo apoptosis, dramatically reducing blood flow to important parts of the brain and often resulting in death or severe mental and physical changes. [6] Platinum nanoparticles have been shown to act as ROS, serving as “biological antioxidants” and significantly reducing oxidation in the brain as a result of stroke. [6] Nanoparticles can also lead to neurotoxicity and cause permanent BBB damage either from brain oedema or from unrelated molecules crossing the BBB and causing brain damage. [5] This proves further long term in vivo studies are needed to gain enough understanding to allow for successful clinical trials.

One of the most common nano-based drug delivery platforms is liposome-based delivery. They are both lipid-soluble and nano-scale and thus are permitted through a fully functioning BBB. Additionally, lipids themselves are biological molecules, making them highly biocompatible, which in turn lowers the risk of cell toxicity. The bilayer that is formed allows the molecule to fully encapsulate any drug, protecting it while it is travelling through the body. One drawback to shielding the drug from the outside cells is that it no longer has specificity, and requires coupling to extra antibodies to be able to target a biological site. Due to their low stability, liposome-based nanoparticles for drug delivery have a short shelf life. [4]

Targeted therapy using magnetic nanoparticles (MNPs) is also a popular topic of research and has led to several stage III clinical trials. [7] Invasiveness is not an issue here because a magnetic force can be applied from the outside of a patient’s body to interact and direct the MNPs. This strategy has been proven successful in delivering brain-derived neurotropic factor, a naturally occurring gene thought to promote neurorehabilitation, across the BBB. [5]

Nano-imaging tools

The visualization of neuronal activity is of key importance in neuroscience. Nano-imaging tools with nanoscale resolution help in these areas. These optical imaging tools are PALM [8] and STORM [9] which helps visualize nanoscale objects within cells. So far, these imaging tools revealed the dynamic behavior and organization of the actin cytoskeleton inside the cells, which will assist in understanding how neurons probe their involvement during neuronal outgrowth and in response to injury, and how they differentiate axonal processes and characterization of receptor clustering and stoichiometry at the plasma inside the synapses, which are critical for understanding how synapses respond to changes in neuronal activity. [1] These past works focused on devices for stimulation or inhibition of neural activity, but the crucial aspect is the ability for the device to simultaneously monitor neural activity. The major aspect that is to be improved in the nano imaging tools is the effective collection of the light as a major problem is that biological tissue are dispersive media that do not allow a straightforward propagation and control of light. These devices use nanoneedle and nanowire for probing and stimulation. [8]

Nanowires

Nanowires are artificial nano- or micro-sized “needles” that can provide high-fidelity electrophysiological recordings if used as microscopic electrodes for neuronal recordings. Nanowires are an attractive as they are highly functional structures that offer unique electronic properties that are affected by biological/chemical species adsorbed on their surface; mostly the conductivity. [10] [11] This conductivity variance depending on chemical species present allows enhanced sensing performances. [12] Nanowires are also able to act as non-invasive and highly local probes. These versatility of nanowires makes it optimal for interfacing with neurons due to the fact that the contact length along the axon (or the dendrite projection crossing a nanowires) is just about 20 nm. [13]

Related Research Articles

Nanomedicine is the medical application of nanotechnology. Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology such as biological machines. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials.

Blood–brain barrier Semipermeable capillary border that allows selective passage of blood constituents into the brain

The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside. The blood–brain barrier is formed by endothelial cells of the capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. This system allows the passage of some molecules by passive diffusion, as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose, water and amino acids that are crucial to neural function.

Small interfering RNA

Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA non-coding RNA molecules, typically 20-27 base pairs in length, similar to miRNA, and operating within the RNA interference (RNAi) pathway. It interferes with the expression of specific genes with complementary nucleotide sequences by degrading mRNA after transcription, preventing translation.

Neurotechnology is any technology that has a fundamental influence on how people understand the brain and various aspects of consciousness, thought, and higher order activities in the brain. It also includes technologies that are designed to improve and repair brain function and allow researchers and clinicians to visualize the brain.

Nanorobotics

Nanorobotics is an emerging technology field creating machines or robots whose components are at or near the scale of a nanometer. More specifically, nanorobotics refers to the nanotechnology engineering discipline of designing and building nanorobots, with devices ranging in size from 0.1 to 10 micrometres and constructed of nanoscale or molecular components. The terms nanobot, nanoid, nanite, nanomachine, or nanomite have also been used to describe such devices currently under research and development.

Dendrimer

Dendrimers are highly ordered, branched polymeric molecules. The name comes from the Greek word δένδρον (dendron) which translates to "tree". Synonymous terms for dendrimer include arborols and cascade molecules. Typically, dendrimers are symmetric about the core, and often adopt a spherical three-dimensional morphology. The word dendron is also encountered frequently. A dendron usually contains a single chemically addressable group called the focal point or core. The difference between dendrons and dendrimers is illustrated in the top figure, but the terms are typically encountered interchangeably.

Nanobiotechnology Intersection of nanotechnology and biology

Nanobiotechnology, bionanotechnology, and nanobiology are terms that refer to the intersection of nanotechnology and biology. Given that the subject is one that has only emerged very recently, bionanotechnology and nanobiotechnology serve as blanket terms for various related technologies.

HIV-associated neurocognitive disorders (HAND) are neurological disorders associated with HIV infection and AIDS. It is a syndrome of progressive deterioration of memory, cognition, behavior, and motor function in HIV-infected individuals during the late stages of the disease, when immunodeficiency is severe. HAND may include neurological disorders of various severity. HIV-associated neurocognitive disorders are associated with a metabolic encephalopathy induced by HIV infection and fueled by immune activation of macrophages and microglia. These cells are actively infected with HIV and secrete neurotoxins of both host and viral origin. The essential features of HIV-associated dementia (HAD) are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change. Cognitive impairment is characterised by mental slowness, trouble with memory and poor concentration. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors. Behavioral changes may include apathy, lethargy and diminished emotional responses and spontaneity. Histopathologically, it is identified by the infiltration of monocytes and macrophages into the central nervous system (CNS), gliosis, pallor of myelin sheaths, abnormalities of dendritic processes and neuronal loss.

Nanochemistry is the combination of chemistry and nano science. Nanochemistry is associated with synthesis of building blocks which are dependent on size, surface, shape and defect properties. Nanochemistry is being used in chemical, materials and physical, science as well as engineering, biological and medical applications. Nanochemistry and other nanoscience fields have the same core concepts but the usages of those concepts are different.

Drug delivery

Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. Principles related to drug preparation, route of administration, site-specific targeting, metabolism, and toxicity are used to optimize efficacy and safety, and to improve patient convenience and compliance. Drug delivery is aimed at altering a drug's pharmacokinetics and specificity by formulating it with different excipients, drug carriers, and medical devices. There is additional emphasis on increasing the bioavailability and duration of action of a drug to improve therapeutic outcomes. Some research has also been focused on improving safety for the person administering the medication. For example, several types of microneedle patches have been developed for administering vaccines and other medications to reduce the risk of needlestick injury.

A biointerface is the region of contact between a biomolecule, cell, biological tissue or living organism or organic material considered living with another biomaterial or inorganic/organic material. The motivation for biointerface science stems from the urgent need to increase the understanding of interactions between biomolecules and surfaces. The behavior of complex macromolecular systems at materials interfaces are important in the fields of biology, biotechnology, diagnostics, and medicine. Biointerface science is a multidisciplinary field in which biochemists who synthesize novel classes of biomolecules cooperate with scientists who have developed the tools to position biomolecules with molecular precision, scientists who have developed new spectroscopic techniques to interrogate these molecules at the solid-liquid interface, and people who integrate these into functional devices.

Nanoparticle–biomolecule conjugate

A nanoparticle–biomolecule conjugate is a nanoparticle with biomolecules attached to its surface. Nanoparticles are minuscule particles, typically measured in nanometers (nm), that are used in nanobiotechnology to explore the functions of biomolecules. Properties of the ultrafine particles are characterized by the components on their surfaces more so than larger structures, such as cells, due to large surface area-to-volume ratios. Large surface area-to-volume-ratios of nanoparticles optimize the potential for interactions with biomolecules.

The applications of nanotechnology, commonly incorporate industrial, medicinal, and energy uses. These include more durable construction materials, therapeutic drug delivery, and higher density hydrogen fuel cells that are environmentally friendly. Being that nanoparticles and nanodevices are highly versatile through modification of their physiochemical properties, they have found uses in nanoscale electronics, cancer treatments, vaccines, hydrogen fuel cells, and nanographene batteries.

Gene therapy is being studied for some forms of epilepsy. It relies on viral or non-viral vectors to deliver DNA or RNA to target brain areas where seizures arise, in order to prevent the development of epilepsy or to reduce the frequency and/or severity of seizures. Gene therapy has delivered promising results in early stage clinical trials for other neurological disorders such as Parkinson's disease, raising the hope that it will become a treatment for intractable epilepsy.

Nanoparticles for drug delivery to the brain is a method for transporting drug molecules across the blood–brain barrier (BBB) using nanoparticles. These drugs cross the BBB and deliver pharmaceuticals to the brain for therapeutic treatment of neurological disorders. These disorders include Parkinson's disease, Alzheimer's disease, schizophrenia, depression, and brain tumors. Part of the difficulty in finding cures for these central nervous system (CNS) disorders is that there is yet no truly efficient delivery method for drugs to cross the BBB. Antibiotics, antineoplastic agents, and a variety of CNS-active drugs, especially neuropeptides, are a few examples of molecules that cannot pass the BBB alone. With the aid of nanoparticle delivery systems, however, studies have shown that some drugs can now cross the BBB, and even exhibit lower toxicity and decrease adverse effects throughout the body. Toxicity is an important concept for pharmacology because high toxicity levels in the body could be detrimental to the patient by affecting other organs and disrupting their function. Further, the BBB is not the only physiological barrier for drug delivery to the brain. Other biological factors influence how drugs are transported throughout the body and how they target specific locations for action. Some of these pathophysiological factors include blood flow alterations, edema and increased intracranial pressure, metabolic perturbations, and altered gene expression and protein synthesis. Though there exist many obstacles that make developing a robust delivery system difficult, nanoparticles provide a promising mechanism for drug transport to the CNS.

Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury, toxic metabolites, or autoimmunity. In the central nervous system (CNS), including the brain and spinal cord, microglia are the resident innate immune cells that are activated in response to these cues. The CNS is typically an immunologically privileged site because peripheral immune cells are generally blocked by the blood–brain barrier (BBB), a specialized structure composed of astrocytes and endothelial cells. However, circulating peripheral immune cells may surpass a compromised BBB and encounter neurons and glial cells expressing major histocompatibility complex molecules, perpetuating the immune response. Although the response is initiated to protect the central nervous system from the infectious agent, the effect may be toxic and widespread inflammation as well as further migration of leukocytes through the blood–brain barrier.

Gold nanoparticles in chemotherapy

Gold nanoparticles in chemotherapy and radiotherapy is the use of colloidal gold in therapeutic treatments, often for cancer or arthritis. Gold nanoparticle technology shows promise in the advancement of cancer treatments. Some of the properties that gold nanoparticles possess, such as small size, non-toxicity and non-immunogenicity make these molecules useful candidates for targeted drug delivery systems. With tumor-targeting delivery vectors becoming smaller, the ability to by-pass the natural barriers and obstacles of the body becomes more probable. To increase specificity and likelihood of drug delivery, tumor specific ligands may be grafted onto the particles along with the chemotherapeutic drug molecules, to allow these molecules to circulate throughout the tumor without being redistributed into the body.

Nano neuro knitting is an emerging technology for repairing nervous system tissues via nano scaffolding techniques. Currently being explored in numerous research endeavors, nano neuro knitting has been shown to allow partial reinnervation in damaged areas of the nervous system through the interactions between potentially regenerative axons and peptide scaffolds. This interaction has been shown to lead to sufficient axon density renewal to the point that functionality is restored. While nano neuro knitting shows promise, the uncertainty of the effects in human subjects warrants further investigation before clinical trials initiate.

Virus nanotechnology is the use of viruses as a source of nanoparticles for biomedical purposes. Viruses are made up of a genome and a capsid; and some viruses are enveloped. Most virus capsids measure between 20-500 nm in diameter. Because of their nanometer size dimensions, viruses have been considered as naturally occurring nanoparticles. Virus nanoparticles have been subject to the nanoscience and nanoengineering disciplines. Viruses can be regarded as prefabricated nanoparticles. Many different viruses have been studied for various applications in nanotechnology: for example, mammalian viruses are being developed as vectors for gene delivery, and bacteriophages and plant viruses have been used in drug delivery and imaging applications as well as in vaccines and immunotherapy intervention.

The blood-spinal cord barrier (BSCB) is a semipermeable anatomical interface that consists of the specialized small blood vessels that surround the spinal cord. While similar to the blood-brain barrier in function and morphology, it is physiologically independent and has several distinct characteristics. The BSCB is involved in many disorders affecting the central nervous system, including neurodegenerative diseases, pain disorders, and traumatic spinal cord injury. In conjunction with the blood-brain barrier, the BSCB contributes to the difficulty in delivering drugs to the central nervous system, which makes drug targeting of the BSCB an important goal in pharmaceutical research.

References

  1. 1 2 Pampaloni, Niccolò Paolo (2019). "Advances in Nano Neuroscience: From Nanomaterials to Nanotools". Frontiers in Neuroscience. 12: 953. doi:10.3389/fnins.2018.00953. PMC   6341218 . PMID   30697140.
  2. 1 2 Dong X (2018). "Current Strategies for Drug Delivery". Theranostics. 8 Suppl1 (6): 1481–1493. doi: 10.7150/thno.21254 . PMC   5858162 . PMID   29556336.
  3. ↑ Gray J (2015). "Viral vectors and delivery strategies for CNS gene therapy". Ther Deliv. 10 Suppl1 (4): 517–534. doi: 10.4155/tde.10.50 . PMC   4509525 . PMID   22833965.
  4. 1 2 Landry, Markita. CBE 182Nanoscience and Engineering Biotechnology (Fall2018 (PDF) (Speech). Lecture. Retrieved April 30, 2020.
  5. 1 2 3 Kumar A (2017). "Nanotechnology for Neuroscience: Promising Approaches for Diagnostics, Therapeutics and Brain Activity Mapping". Adv Funct Mater. 27 Suppl1 (39): 1700489. doi: 10.1002/adfm.201700489 . PMC   6404766 . PMID   30853878.
  6. 1 2 3 Panagiotou Stavros; Saha Sikha (2015). "Therapeutic benefits of nanoparticles in stroke". Frontiers in Neuroscience. 9: 182. doi: 10.3389/fnins.2015.00182 . PMC   4436818 . PMID   26041986.
  7. ↑ Paige P (2018). "Magnetic Drug Delivery: Where the Field is Going". Frontiers in Neuroscience. 6 Suppl1: 619. Bibcode:2018FrCh....6..619P. doi: 10.3389/fchem.2018.00619 . PMC   6297194 . PMID   30619827.
  8. 1 2 Pisanello, F. (2016). "Micro- and nanotechnologies for optical neural interfaces". Frontiers in Neuroscience. 10: 70. doi:10.3389/fnins.2016.00070. PMC   4781845 . PMID   27013939.
  9. ↑ Alivisatos, A. P. (2013). "Nanotools for neuroscience and brain activity mapping". ACS Nano. 7 (3): 1850–1866. doi:10.1021/nn4012847. hdl:1721.1/79786. PMC   3665747 . PMID   23514423.
  10. ↑ Vidu, Rahman (2014). "Nanostructures: a platform for brain repair and augmentation". Frontiers in Systems Neuroscience. 8: 91. doi:10.3389/fnsys.2014.00091. PMC   4064704 . PMID   24999319.
  11. ↑ Wu, Y. (2004). "Controlled growth and structures of molecular-scale silicon nanowires". Nano Lett. 4 (3): 433–436. Bibcode:2004NanoL...4..433W. doi:10.1021/nl035162i.
  12. ↑ Ahmad, Rafiq; Mahmoudi, Tahmineh; Ahn, Min-Sang; Hahn, Yoon-Bong (2018). "Recent advances in nanowires-based field-effect transistors for biological sensor applications". Biosensors and Bioelectronics. 100: 312–325. doi:10.1016/j.bios.2017.09.024. PMC   7126762 . PMID   28942344.
  13. ↑ Vidu, Rahman (2014). "Nanostructures: a platform for brain repair and augmentation". Frontiers in Systems Neuroscience. 8. doi:10.3389/fnsys.2014.00091. PMC   4064704 . PMID   24999319.
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