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Aptamer Nanoconstructs Crossing Human Blood-Brain Barrier Discovered via Microphysiological System-Based SELEX
Jeong-Won Choi1, Minwook Seo1, Kyunghwan Kim2
1Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea 44919.
ACS Nano
|April 17, 2023
Summary
Researchers developed a new method using a human microphysiological system (MPS) to discover aptamers that can effectively deliver drugs across the blood-brain barrier (BBB). This approach enhances brain drug delivery for neurological therapeutics.
Area of Science:
- Biotechnology
- Neuroscience
- Drug Delivery
Background:
- The blood-brain barrier (BBB) presents a significant obstacle for neurological therapeutics.
- Aptamers are promising for BBB drug delivery, but traditional selection methods lack physiological relevance.
- Existing methods for identifying BBB-penetrating aptamers are challenged by poor human physiological relevance.
Purpose of the Study:
- To develop and validate a novel aptamer selection method for efficient human BBB drug delivery.
- To identify a human BBB shuttle aptamer (hBS) using a microphysiological system (MPS)-based SELEX (MPS-SELEX) approach.
Main Methods:
- Utilized a two-channel human MPS with brain microvascular endothelial cells, astrocytes, and pericytes to model the BBB.
- Employed a function-based screening approach, MPS-SELEX, for aptamer selection.
- Validated the identified aptamer's (hBS01) transport capability, uptake efficiency, and targeting specificity in vitro and in vivo.
Main Results:
- Identified a human BBB shuttle aptamer (hBS01) through five rounds of MPS-SELEX.
- hBS01 demonstrated efficient protein cargo transport across the human BBB via clathrin-mediated endocytosis.
- hBS01 showed enhanced uptake in brain cells and validated targeting specificity, confirming strong brain accumulation.
Conclusions:
- MPS-SELEX is a powerful platform for discovering aptamers with high target specificity for BBB penetration.
- The identified hBS01 aptamer holds significant potential for enhancing drug delivery strategies for neurological disorders.
- This method overcomes limitations of traditional SELEX, offering improved physiological relevance for aptamer discovery.
