Laser and Gold Nanoparticles: Breaking the Blood-Brain Barrier for Faster Drug Delivery
Written by | Xiao XiaEdited by | Wang DuoyuFormatted by | Shui ChengwenBlood-Brain Barrier (BBB) is the barrier formed between the plasma and brain cells by the walls of brain capillaries and glial cells, and the barrier formed between plasma and cerebrospinal fluid by the choroid plexus, only allowing specific types of molecules from the bloodstream to enter brain neurons and other surrounding cells.The existence of the blood-brain barrier is significant for preventing harmful substances from entering the brain from the blood; however, it also restricts the transfer of most small and large molecules (such as peptides, proteins, and nucleic acids), severely limiting the treatment of central nervous system diseases (such as neurodegenerative diseases, brain tumors, brain infections, and strokes).With the increasingly serious issue of population aging, neurodegenerative diseases such as Alzheimer’s disease are rapidly increasing, and the treatment of brain diseases faces severe challenges; thus, there is an urgent need for effective drug delivery strategies that can break the blood-brain barrier.Due to their unique physical and chemical properties, gold nanoparticles (AuNPs) have attracted great interest in diagnostics, imaging, and therapeutics in the biomedical field. By using nanosecond laser pulses to perform nanoscale restricted heating on AuNPs, selective and remote inactivation of target proteins can be achieved.On November 13, 2021, a research team from the University of Texas at Dallas and the Southwestern Medical Center published a research paper titled: Reversibly Modulating the Blood–Brain Barrier by Laser Stimulation of Molecular-Targeted Nanoparticles in the journal Nano Letters.The researchers synthesized gold nanoparticles specifically targeting tight junctions and demonstrated that transcranial picosecond laser stimulation of the nanoparticles after intravenous injection increased the permeability of the blood-brain barrier.This study developed targeted gold nanoparticles (AuNPs) for cell tight junctions, which, after intravenous injection, were subjected to transcranial picosecond (trillionths of a second) laser stimulation, thereby temporarily opening the blood-brain barrier, allowing drugs to enter the brain through the bloodstream. This technology for regulating the blood-brain barrier is reversible and does not damage the neurovascular structure. This technology will aid in the treatment of neurological diseases such as brain tumors, amyotrophic lateral sclerosis, and strokes.The research team first synthesized a complex of gold nanoparticles targeting cell tight junctions, which consisted of AuNPs modified with junctional adhesion molecule A (JAM-A) and the BV11 antibody. By intravenously injecting AuNP-BV11 into mice, they observed that AuNP-BV11 co-localized with cell tight junctions. At the same time, the half-life of AuNP-BV11 was very short, only 10 minutes, and long-term injection did not cause systemic toxicity. These results indicate that systemic administration of AuNP-BV11 can selectively target the blood-brain barrier along the luminal surface of the brain vascular system without significant toxicity.Next, the research team characterized changes in blood-brain barrier permeability under remote laser stimulation. One hour after administration, applying a 532 nm picosecond laser, they found that the laser excited the cell tight junction-targeted AuNP-BV11 while temporarily increasing the permeability of the blood-brain barrier.Cerebral arterioles strictly regulate blood flow through vascular dilation. Disruption of vascular dilation may impair the supply of oxygen and nutrients to local brain regions. The research team examined the vascular dilation before and after regulating the blood-brain barrier and found that regulating the blood-brain barrier did not affect arteriolar vascular dilation, and the structural integrity of the vascular system and brain parenchyma remained well preserved.Finally, the research team tested the therapeutic capabilities of this new technology to deliver antibodies, adenoviruses, and liposomes. Analysis indicated that the antibody concentration intensity in the laser-treated area was significantly higher than in the non-laser area; the delivery of adenoviral vectors with GFP resulted in 64% of cortical neurons in the same hemisphere expressing GFP clearly; and the fluorescence intensity of DIL-liposomes in the laser-treated area was higher than that in the opposite hemisphere. Therefore, regulating the blood-brain barrier allowed antibodies, adenoviral vectors, and liposomes to penetrate into the brain and showed significant therapeutic potential.In summary, this work developed a new brain delivery technology consisting of two parts: one is picosecond laser, and the other is targeted gold nanoparticles for cell tight junctions. This technology only requires intravenous injection of gold nanoparticles into the body, followed by picosecond laser irradiation in the target area, temporarily opening the blood-brain barrier and helping drugs to break through the blood-brain barrier to reach the brain. This work is expected to benefit many patients troubled by central nervous system disease treatments.Paper Link:https://pubs.acs.org/doi/full/10.1021/acs.nanolett.1c02996
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