UNIST Develops Blood-Brain Barrier Penetrating Aptamer... "Trojan Horse, Effective Drug Delivery"

The research team led by Professors Tae-Eun Park and Jin-Myung Joo from the Department of Biomedical Engineering at UNIST has developed a ‘blood-brain barrier (BBB) permeable aptamer’ capable of delivering drugs to the brain using an artificial blood-brain barrier chip.

The blood-brain barrier (BBB) is a biological barrier that strictly regulates the homeostasis of the central nervous system (CNS).

The BBB allows only substances essential for brain function to pass through, protecting the brain from external substances. However, this system also controls drugs intended to treat brain diseases, posing a significant obstacle to drug therapy.

Currently, the ‘Trojan horse strategy’ is mainly used to effectively deliver drugs for brain disease treatment to the brain.

The Trojan horse strategy involves introducing molecules that target receptors or transport proteins expressed on brain vascular endothelial cells into drugs, enabling drugs that cannot normally cross the blood-brain barrier to be easily absorbed by cells and transported into the brain.

Recently, one of these targeting molecules gaining attention is the ‘aptamer.’ Aptamers are short nucleotide strands with a three-dimensional structure that have high binding affinity to target cells or biological tissues.

Aptamers are replacing antibodies and peptides, which were previously used as targeting molecules, due to their advantages such as low cost, small size, and low immunogenicity.

Existing blood-brain barrier permeable aptamers have been developed using in vitro models or animal models, but these models have limitations in replicating actual biological functions and face difficulties in developing effective brain-targeting molecules due to interspecies differences.

Schematic diagram of blood-brain barrier permeable aptamer development using artificial blood-brain barrier chip.

To address this, the UNIST research team utilized a self-developed ‘artificial blood-brain barrier chip’ to develop aptamers that can penetrate the blood-brain barrier and drug delivery technology using these aptamers.

The artificial blood-brain barrier chip used for aptamer development consists of two microchannels. One channel mimics blood vessels using brain vascular endothelial cells derived from induced pluripotent stem cells, while the other channel co-cultures astrocytes and pericytes to simulate the brain environment.

This model has a barrier level comparable to that of living organisms and simulates the flow of fluids similar to blood, enabling the selection of aptamers targeting the blood-brain barrier in a realistic biological environment.

The research team introduced random sequence aptamers into the blood vessels of the fabricated blood-brain barrier and repeatedly selected aptamer sequences that penetrated the barrier and were delivered into the brain, thereby isolating aptamers with high blood-brain barrier permeability.

The selected aptamer (hBS01) showed 2 to 3 times higher permeability efficiency compared to other aptamers.

The research team explained, “Compared to random aptamers, hBS01 exhibited specifically high absorption and permeability efficiency only in brain vascular cell models, as well as high permeability efficiency in major brain constituent cells.”

They added, “This can be utilized not only for developing therapeutics for brain-related diseases such as dementia and brain tumors but also as a strategy to improve brain delivery efficiency of various drug candidates that failed clinical trials due to blood-brain barrier permeability issues.”

To confirm the potential of hBS01 as a drug delivery vehicle, the research team created nanoparticles coated with hBS01 on their surface. When these nanoparticles were injected into experimental animals, they showed high accumulation efficiency in the brain, confirming that drug delivery vehicles using hBS01 are effective even in clinical trials.

Jungwon Choi, the first author of the paper, stated, “This study has opened new possibilities for delivering drugs to the brain,” and added, “If various artificial organ chips are utilized, it is expected to be more broadly applied to the development of drug delivery vehicles targeting various organs.”

This research was conducted by the research team of Professors Tae-Eun Park and Jin-Myung Joo from the Department of Biomedical Engineering and was supported by the Dementia Overcoming R&D Project, the National Research Foundation of Korea’s Excellent New Researcher Support Project, Basic Research Laboratory Support Project, and the Pan-Government Regenerative Medicine Technology Development Project.

The research results were published online on April 17 in ACS NANO, a prestigious journal in the field of nanoscience.

This content was produced with the assistance of AI translation services.