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Laser Plus Gold Nanoparticles: Contributing to Faster Drug Delivery  

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Jerry Carter

The blood-brain barrier (BBB) is the barrier between plasma and brain cells formed by the walls of brain capillaries and glial cells, and between plasma and cerebrospinal fluid formed by the choroid plexus, allowing only specific types of molecules to enter the brain neurons and other surrounding cells from the bloodstream.

 

The existence of the blood-brain barrier is important in preventing the entry of harmful substances from the blood into the brain; however, it also prevents the transfer of the vast majority of small and large molecules (e.g., peptides, proteins, and nucleic acids), severely limiting the treatment of diseases of the central nervous system (e.g., neurodegenerative diseases, brain tumors, brain infections, and strokes).

 

With the aging population, neurodegenerative diseases such as Alzheimer's disease are on the rise, and treating brain disorders is proved difficult. As a result, drug delivery systems that efficiently penetrate the BBB are in high demand.

 

Gold nanoparticles (AuNPs) have sparked great interest in diagnostics, imaging, and therapies in the biomedical area due to their unique physical and chemical features. Nanoscale restricted heating of AuNPs using nanosecond laser pulses can be used to selectively and remotely deactivate proteins of interest.

 

Nov. 13, 2021—A team of researchers from the University of Texas at Dallas and Southwestern Medical Center published a research paper in the journal Nano Letters titled: Reversibly Modulating the Blood-Brain Barrier by Laser Stimulation of Molecular-Targeted Nanoparticles.

 

The researchers synthesized gold nanoparticles to specifically target tight junctions and demonstrated that transcranial picosecond laser stimulation of nanoparticles after intravenous injection increased the permeability of the blood-brain barrier.

 

The study developed AuNPs that target tightly linked cells, and after intravenous injection, these gold nanoparticles were subjected to transcranial picosecond (trillionth of a second) laser stimulation, which temporarily opens the blood-brain barrier and allows the drug to enter the brain through the bloodstream. This technique modulates the blood-brain barrier in a reversible manner and does not disrupt neurovascular structures, and will be useful in the treatment of neurological diseases such as brain tumors, acromegaly, and stroke.

 

The scientists first developed gold nanoparticle complexes including Junction Adhesion Molecule A (JAM-A) and BV11 antibody-modified AuNP that target cellular tight junction. They detected tightly connected co-localization of AuNP-BV11 with cells after giving AuNP-BV11 to mice intravenously. Meanwhile, AuNP-BV11 has a short half-life of only 10 minutes, and long-term injection did not induce systemic toxicity. These findings show that systemic AuNP-BV11 treatment preferentially targets the blood-brain barrier along the luminal surface of the cerebral vascular system with no apparent toxicity.

 

The researchers next looked at how the blood-brain barrier permeability changed as a result of remote laser stimulation. They discovered that laser excitation of cells strongly associated to targeted AuNP-BV11 was accompanied with a temporary increase in the permeability of the blood-brain barrier 1 hour after administration when they used a 532 nm picosecond laser.

 

Vasodilation in the small cerebral arteries firmly controls blood flow. The supply of oxygen and nutrients to local brain regions may be harmed if vasodilation is disrupted. The researchers looked at vasodilation before and after modulating the blood-brain barrier and discovered that modulating the blood-brain barrier had no effect on small artery vasodilation and that the vascular system and brain parenchyma were structurally intact.

 

Finally, the researchers looked at how well this novel method could transport antibodies, adenovirus, and liposomes for therapeutic purposes. The intensity of antibody concentration was much higher in laser-treated areas than in non-laser areas, and adeno-associated virus delivery with GFP allowed 64% of cortical neurons to clearly express GFP in the ipsilateral hemisphere. DIL-liposome fluorescence intensity was also higher in laser-treated areas than in the contralateral hemisphere. Antibodies, adeno-associated viruses, and liposomes were able to penetrate the blood-brain barrier, indicating that manipulation of the barrier has great therapeutic potential.

 

In summary, the research has created a new brain delivery system consisting of two components: a picosecond laser and gold nanoparticles that target cells in close proximity. This method entails injecting gold nanoparticles into the body and then applying a picosecond laser to the target area to briefly open the blood-brain barrier, allowing the drug to pass through and reach the brain. This work is expected to benefit many patients suffering from the treatment of central nervous system diseases.

 

 

 

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Jerry Carter
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