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Written by xiao xia Edited by Wang Duoyu | Water-written blood-brain barrier (BBB) refers to the barrier between the blood plasma and brain cells formed by the brain capillary wall and glial cells, and the plasma and cerebrospinal fluid formed by the choroid plexus The barrier between them allows 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 of great significance in preventing harmful substances from entering the brain from the blood.
However, the blood-brain barrier also prevents the transfer of most small and macromolecules (such as peptides, proteins and nucleic acids), which severely restricts the nerves.
Treatment of central system diseases (such as neurodegenerative diseases, brain tumors, brain infections and strokes, etc.
)
.
With the increasingly serious population aging problem, neurodegenerative diseases such as Alzheimer's disease are growing rapidly, and the treatment of brain diseases is facing severe challenges.
Therefore, there is an urgent need for drug delivery strategies that effectively break through the blood-brain barrier
.
Due to unique physical and chemical properties, gold nanoparticles (AuNPs) have aroused great interest in diagnostics, imaging and therapeutics in the field of biomedicine
.
By using nanosecond laser pulses to conduct nanoscale restricted heating of AuNPs, selective and remote inactivation of the protein of interest can be achieved
.
On November 13, 2021, a research team from the University of Texas at Dallas and Southwestern Medical Center published a research paper titled: Reversibly Modulating the Blood–Brain Barrier by Laser Stimulation of Molecular-Targeted Nanoparticles in Nano Letters
.
The researchers synthesized gold nanoparticles to specifically target tight junctions and demonstrated that transcranial picosecond laser stimulation of the nanoparticles after intravenous injection increases the permeability of the blood-brain barrier
.
The research has developed gold nanoparticles (AuNPs) that target tightly connected cells.
After intravenous injection, these gold nanoparticles are subjected to transcranial picosecond (one trillionth of a second) laser stimulation to temporarily open the blood-brain barrier , So that the drug can enter the brain through the blood
.
The regulation of the blood-brain barrier by this technology is reversible and will not damage the neurovascular structure
.
This technology will help the treatment of neurological diseases such as brain tumors, frostbite, and stroke
.
The research team first synthesized a gold nanoparticle complex that targets the Tight Junction of cells.
This complex is composed of AuNP modified with the adhesion molecule A (JAM-A) and the BV11 antibody
.
By injecting AuNP-BV11 intravenously into mice, they observed that AuNP-BV11 co-localizes with the tight cell link
.
At the same time, the half-life of AuNP-BV11 is very short, only 10 minutes, and long-term injection will not cause systemic toxicity
.
These results indicate that the systemic administration of AuNP-BV11 can selectively target the blood-brain barrier along the luminal surface of the cerebral vascular system without significant toxicity
.
Next, the research team characterized the changes in the permeability of the blood-brain barrier under remote laser stimulation
.
Applying a 532 nm picosecond laser 1 hour after the administration, they found that the laser stimulated the cell-tight junction targeting AuNP-BV11, and at the same time the permeability of the blood-brain barrier was temporarily increased
.
Cerebral arterioles strictly regulate blood flow through vasomotor
.
The interruption of vasomotor may impair the oxygen and nutrient supply to the local brain area
.
The research team checked the vasomotor conditions before and after adjusting the blood-brain barrier, and found that adjusting the blood-brain barrier did not affect the vasomotion of small arteries, and the structural integrity of the vascular system and brain parenchyma was maintained well
.
Finally, the research team tested the ability of this new technology to deliver antibodies, adenoviruses and liposomes
.
The analysis showed that the antibody concentration in the laser-treated area was much higher than that in the non-laser area; the delivery of adeno-associated virus with GFP made 64% of cortical neurons clearly express GFP in the ipsilateral hemisphere; the DIL-liposome fluorescence in the laser-treated area The intensity is higher than the contralateral hemisphere
.
Therefore, regulating the blood-brain barrier allows antibodies, adeno-associated viruses and liposomes to penetrate into the brain and shows significant therapeutic potential
.
In summary, this work has developed a new brain delivery technology that consists of two parts: one is a picosecond laser, and the other is gold nanoparticles that target tightly connected cells
.
This technology only needs to inject gold nanoparticles into the body through a vein, and then irradiate the target area with picosecond laser, which can temporarily open the blood-brain barrier and help the drug to break through the blood-brain barrier and reach the brain
.
This work is expected to benefit many patients suffering from the treatment of central nervous system diseases
.
Link to the paper: https://pubs.
acs.
org/doi/full/10.
1021/acs.
nanolett.
1c02996 is open for reprinting, welcome to forward to Moments and WeChat groups
.
The existence of the blood-brain barrier is of great significance in preventing harmful substances from entering the brain from the blood.
However, the blood-brain barrier also prevents the transfer of most small and macromolecules (such as peptides, proteins and nucleic acids), which severely restricts the nerves.
Treatment of central system diseases (such as neurodegenerative diseases, brain tumors, brain infections and strokes, etc.
)
.
With the increasingly serious population aging problem, neurodegenerative diseases such as Alzheimer's disease are growing rapidly, and the treatment of brain diseases is facing severe challenges.
Therefore, there is an urgent need for drug delivery strategies that effectively break through the blood-brain barrier
.
Due to unique physical and chemical properties, gold nanoparticles (AuNPs) have aroused great interest in diagnostics, imaging and therapeutics in the field of biomedicine
.
By using nanosecond laser pulses to conduct nanoscale restricted heating of AuNPs, selective and remote inactivation of the protein of interest can be achieved
.
On November 13, 2021, a research team from the University of Texas at Dallas and Southwestern Medical Center published a research paper titled: Reversibly Modulating the Blood–Brain Barrier by Laser Stimulation of Molecular-Targeted Nanoparticles in Nano Letters
.
The researchers synthesized gold nanoparticles to specifically target tight junctions and demonstrated that transcranial picosecond laser stimulation of the nanoparticles after intravenous injection increases the permeability of the blood-brain barrier
.
The research has developed gold nanoparticles (AuNPs) that target tightly connected cells.
After intravenous injection, these gold nanoparticles are subjected to transcranial picosecond (one trillionth of a second) laser stimulation to temporarily open the blood-brain barrier , So that the drug can enter the brain through the blood
.
The regulation of the blood-brain barrier by this technology is reversible and will not damage the neurovascular structure
.
This technology will help the treatment of neurological diseases such as brain tumors, frostbite, and stroke
.
The research team first synthesized a gold nanoparticle complex that targets the Tight Junction of cells.
This complex is composed of AuNP modified with the adhesion molecule A (JAM-A) and the BV11 antibody
.
By injecting AuNP-BV11 intravenously into mice, they observed that AuNP-BV11 co-localizes with the tight cell link
.
At the same time, the half-life of AuNP-BV11 is very short, only 10 minutes, and long-term injection will not cause systemic toxicity
.
These results indicate that the systemic administration of AuNP-BV11 can selectively target the blood-brain barrier along the luminal surface of the cerebral vascular system without significant toxicity
.
Next, the research team characterized the changes in the permeability of the blood-brain barrier under remote laser stimulation
.
Applying a 532 nm picosecond laser 1 hour after the administration, they found that the laser stimulated the cell-tight junction targeting AuNP-BV11, and at the same time the permeability of the blood-brain barrier was temporarily increased
.
Cerebral arterioles strictly regulate blood flow through vasomotor
.
The interruption of vasomotor may impair the oxygen and nutrient supply to the local brain area
.
The research team checked the vasomotor conditions before and after adjusting the blood-brain barrier, and found that adjusting the blood-brain barrier did not affect the vasomotion of small arteries, and the structural integrity of the vascular system and brain parenchyma was maintained well
.
Finally, the research team tested the ability of this new technology to deliver antibodies, adenoviruses and liposomes
.
The analysis showed that the antibody concentration in the laser-treated area was much higher than that in the non-laser area; the delivery of adeno-associated virus with GFP made 64% of cortical neurons clearly express GFP in the ipsilateral hemisphere; the DIL-liposome fluorescence in the laser-treated area The intensity is higher than the contralateral hemisphere
.
Therefore, regulating the blood-brain barrier allows antibodies, adeno-associated viruses and liposomes to penetrate into the brain and shows significant therapeutic potential
.
In summary, this work has developed a new brain delivery technology that consists of two parts: one is a picosecond laser, and the other is gold nanoparticles that target tightly connected cells
.
This technology only needs to inject gold nanoparticles into the body through a vein, and then irradiate the target area with picosecond laser, which can temporarily open the blood-brain barrier and help the drug to break through the blood-brain barrier and reach the brain
.
This work is expected to benefit many patients suffering from the treatment of central nervous system diseases
.
Link to the paper: https://pubs.
acs.
org/doi/full/10.
1021/acs.
nanolett.
1c02996 is open for reprinting, welcome to forward to Moments and WeChat groups
