The results of the study showed that the human serum albumin drug delivery nanosystem could significantly improve the efficiency of therapeutic drugs into the brain and the ability to retain in the brain. Mouse models of Alzheimer's disease showed that the nanodrug improved neuronal morphological changes, saved memory impairment, and slowed the onset of the disease.
For a long time, when the brain needs to be treated with drugs due to diseases, it is a very difficult task to deliver the drugs to the brain tissue needed by oral or intravenous injection due to the presence of the blood-brain barrier.
On April 10, the reporter learned from Tianjin University that Professor Chang Jin, director of the Institute of Nano biomedicine in the School of Life Sciences of the university, found another way to drip nanoparticle drugs from the nasal cavity, and found a "shortcut" for the drugs to bypass the blood-brain barrier and enter the brain. At present, the research has made new progress.
The blood-brain barrier is the "copper wall" that guards the brain
Drugs that usually treat brain disease require oral or intravenous injections, and the blood-brain barrier is the only way for these drugs to enter the brain to reach the lesion.
Over the past few decades, scientists have identified the biological pathways that lead to neurodegenerative diseases and developed molecular preparations that target these pathways. However, clinical progress has been extremely slow, in part due to the challenges faced by drugs as they cross the blood-brain barrier.
What exactly is the "iron wall" of the blood-brain barrier that makes drug molecules so insurmountable?
"In layman's terms, the blood-brain barrier is the 'gate' of the brain." Xue Xue, a researcher at the State Key Laboratory of Medicinal Chemical Biology of Nankai University, introduced that the blood-brain barrier is one of the important self-protection mechanisms of human beings, which is composed of brain capillary endothelial cells, glial cells and choroid plexuses, and only allows specific types of molecules to enter brain neurons and other peripheral cells from the blood, which can prevent a variety of harmful substances from entering brain tissue. As the "confidential place" of the human body, the brain controls many important functions of the human body, and the blood-brain barrier can block harmful substances in the blood and protect the safety of brain tissue. But this also means that it also prevents most small molecule drugs, large molecule peptides, proteins, and genetic drugs from entering the brain, severely limiting the treatment of diseases of the nervous center.
Nanoparticles "attack" the blood-brain barrier to deliver drugs
How to cross the blood-brain barrier to deliver drugs to the brain to act on lesions has become a difficult problem faced by the medical community.
Earlier this year, Science Advances, a sub-journal of Science, published a research paper in which scientists at Harvard Medical School and the Massachusetts Institute of Technology used nanoparticles to break through the blood-brain barrier, providing a promising new approach to solving the problem of drugs entering the brain.
The team found that secondary injuries associated with traumatic brain injury can lead to Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. Previously developed methods of delivering therapeutic drugs into the brain after traumatic brain injury rely on a short window of temporary destruction of the blood-brain barrier after trauma, and effective drug delivery tools are lacking after the blood-brain barrier is repaired. The nanoparticle delivery platform developed by scientists can not only be used to deliver protein inhibitors, but also for delivering a variety of drugs, including antibiotics, anti-tumor drugs, neuropeptides, etc. The research team said that while the results were explored and developed using a model of traumatic brain injury, basically neurological disorders could benefit from this work.
On March 10, in the science sub-journal "Science Translational Medicine", researchers from Northwestern University in the United States posted that they have developed a spherical nucleic acid drug, which is made of core nanoparticles combined with targeted small molecule interfering RNA (siRNA), through the precise design of the nanoparticle surface active agents and receptors, the drug can cross the blood-brain barrier after intravenous systemic administration, promote the death of tumor cells.
"These surfactants and receptors are like the nanocarrier 'soldiers' to attack the 'wall' of the blood-brain barrier, and by screening the appropriate 'weapons' and carrying the 'number of weapons', the nanocarrier 'soldiers' have successfully achieved the maximum siRNA encapsulation and the cross-efficiency of the blood-brain barrier, thus achieving a good therapeutic effect on the damaged brain." Xue Xue introduced.
Also using nanoparticles as carriers, Xue Xue's team developed a galactose-modified "triple interaction" stable polymeric siRNA nanodrug, using fasting and glucose supplementation to control blood glucose changes, a biological strategy that triggers the glucose transporter 1 (Glut1) cycle on cerebrovascular endothelial cells, Glut1 specifically recognizes polymeric siRNA nanomoids, through transporter-mediated endocytosis. Enables the migration of polymerized siRNA nanomoids from the cerebrovascular endothelial cell lumen surface to the basal surface, enhancing the delivery of siRNAs in the blood-brain barrier.
"Studies have shown that polymerized siRNA nanodugs have good blood stability and can effectively penetrate the blood-brain barrier through glut1-mediated transport controlled by blood glucose." Xue Xue introduced that in order to confuse the "guards" of the blood-brain barrier and increase the efficiency of passage, the research team also increased camouflage, camouflaging the polymeric siRNA nanodrugs as red blood cell membranes.
Industry experts said that the current research on the use of nanoparticles as a carrier to deliver drugs to the brain is quite promising, and scientists have also placed high hopes on nanoparticles to break through the blood-brain barrier.
There is still a long way to go before clinical application
However, at present, most of the nanoparticle technology is still in the stage of animal experiments, many mechanisms are not particularly clear, and the safety of its clinical application has also been questioned by scientists. For example, the use of metals such as gold as nanoparticle carriers may not be a problem for short-term use. However, the treatment of Alzheimer's disease, Parkinson's disease and other diseases, may require patients to take long-term medication, the accumulation of gold elements in the brain, in what way to metabolize from the human body is a problem.
In recent years, The team of Professor Changjin of Tianjin University has taken a different approach, using nanoparticles made of human serum albumin to carry drugs, trying to drip drugs from the nasal cavity, bypassing the blood-brain barrier to "cut a shortcut" into the brain, and finding a "shortcut" for drugs to treat brain diseases.
The team grasped the currently recognized possible factors that induce Alzheimer's disease, namely Aβ amyloid deposition and acetylcholine imbalance triggered by metal ion aggregation, and proposed the need for a combination treatment that can both inhibit and reduce metal ion aggregation and regulate acetylcholine imbalance to achieve the treatment of the disease.
Among the existing drugs, the research team selected two drugs, chloroiodoxyquine and donepezil, and loaded them into nanoparticles made of human serum albumin. "The nanoparticles we develop have good biosafety." Wu Xiaoli, a researcher in the research team, introduced that in order to target the treatment foci across the natural barrier of the nasal mucosa, the researchers also added two special "small equipment" to the nanoparticles: one is a transmembrane peptide (TAT) that can cross the nasal mucosa, which can improve the efficiency of the nanoparticles across the nasal mucosa; the other is the targeted preparation ganglioside (GM1), which can help drugs that have crossed the nasal mucosa to quickly accumulate to the lesion site in the brain.
The results of the study showed that the serum albumin drug delivery nanosystem of the human serum significantly improved the efficiency of the therapeutic drug into the brain and the ability to retain in the brain. Mouse models of Alzheimer's disease showed that the nanodrug improved neuronal morphological changes, saved memory impairment, and slowed the onset of the disease.
"In the future, nanoparticles can be used as a carrier platform to carry a variety of drugs. At the same time, various targets are loaded on the nanoparticles to make the drug delivery more precise. Wu Xiaoli introduced that her research team currently combines nanotechnology with targeted controlled release, optogenetics, acoustic genetics and other technologies, synthesized a variety of nanomaterials with excellent characteristics, and independently developed a series of multimodal probe-guided visual nanomedicines, which can be applied to the visual treatment of a variety of diseases.
Although the technology is still a long way from being truly applied to the clinic, it can be said that nanoparticles have embarked on a new journey of delivering drugs to the brain. (Chen Xi)
Source: Science and Technology Daily