Nov 29, 2021
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Would you like to take a nano-taxi? These are not small vehicles to shuttle you around town, but tiny, nanometer-scale “vehicles” that mimic nature and are able to target specific nerve cells.

 

This tool, developed at the Technion-Israel Institute of Technology in Haifa, paves the way for the treatment of multiple neurodegenerative diseases and traumatic brain injuries.  

 

Technion assistant Prof. Assaf Zinger and Dr. Caroline Cvetkovic from the Center for Neuroregeneration at the Houston Methodist Research Institute in Texas have created a novel means of delivering medicine to neurons in a targeted manner. Their findings were recently published in the journal Advanced Science under the title “Potentially revolutionizing the treatment of neurodegenerative disorders and traumatic brain injuries.” 

 

Drug delivery is a major challenge that has to be overcome in drug development, and it is one of the focus areas of the Technion’s Wolfson Faculty of Chemical Engineering. It is not enough that a substance can lead to the desired therapeutic effect in a specific cell. This therapeutic substance must also reach these cells without being changed or destroyed along the way – and it must not end up in other organs if it might cause harm there.


Explaining what led him to this study, Zinger recalled, “One Saturday, my family and I were dining with friends. Their little girl has a neurodegenerative disorder; she can’t speak and also has a motor disorder. I wanted to help her.”

Assistant Prof. Assaf Zinger (Credit to Technion-Israel Institute of Technology)

Zinger was already working on various types of biomimetic nano-vesicles, which are similar in their basic structure to human cells but much smaller – one millionth of a hair’s width in diameter. They can carry within them cargo that needs to be delivered to the cells – medication, mRNA and more.

 

Restoration of neural function after traumatic injury, neurodegeneration or neuroinflammation is currently hindered by a lack of effective and clinically practicable biotechnologies for precise, cell-targeted therapies or diagnostics, they wrote.

 

“As such, there remains a need for biotechnological breakthroughs that can enhance and sustain the delivery of therapeutic cargos hile also mimicking the microenvironment of the brain to avoid foreign body response. One promising pathway is the utilization of nanotechnologies inspired by nature, more commonly referred to as bio-inspired or biomimetic tools. By mimicking the composition and biological functions of the cells in our body, biomimetic tools avoid potential side effects that occur from systemic administration of potential therapeutics or imaging tools, such as the inflammation that can occur when using viral-based delivery approaches.” 

 

The targeting of these nano-vesicles is achieved by incorporating specific cell membrane-derived proteins on their surface, thus letting them be recognized and taken in by the correct cells. These specific proteins that cover the surface of these nano-vesicles are naturally used by the body to identify its cells and this is what biomimicry is all about. 

 

In essence, the nanovesicles (or taxis) masquerade as neurons, resulting in their being recognized and welcomed by other neurons, making it possible for them to deliver their therapeutic cargo. 

 

These findings have broad implications. More than one neurodegenerative disorder might be treated if the correct medicine or genetic cargo (such as mRNA, SiRNA, miRNA) could be delivered to the brain. But these are not the only possible applications.

 

“With this, we can also potentially revolutionize the treatment of traumatic brain injuries,” Zinger continued. “In the case of a car accident and or a sports injury, as examples, the brain is first damaged by the impact, as it is struck against the skull. As a result, multiple brain cells are damaged. This starts a process of inflammation. If we could immediately deliver anti-inflammatory drugs to the brain, we could reduce the inflammatory processes and, it is hoped, prevent deaths and long-term disabilities.”


Zinger conducted the vast majority of this study at the Houston Methodist Research Institute and Houston Methodist Hospital as part of his postdoctoral fellowship. He recently opened a multidisciplinary lab at the Wolfson Faculty of Chemical Engineering in Haifa.  His lab aims to create advanced bioinspired technologies and translational therapeutics through a highly multidisciplinary approach.

Specifically, Zinger’s group will integrate can include in vitro (work performed outside of a living organism such as studying cells in culture) and in vivo (research done with or within an entire living organism) models with imaging, molecular biology and chemical techniques to design novel nano-based technologies. These will achieve organ- and cell-specific targeting for improved therapeutic outcomes in different brain and neural diseases, injuries and various cancers.