Exosomes are tiny sacs of about 30 to 150 nanometers in diameter, which are secreted by almost all cells. Containing DNA and proteins and reflecting the state of the cells secreting them, exosomes have been considered promising targets in liquid biopsies capable of diagnosing cancer and other diseases simply by examining body fluids. However, body fluids contain mixtures of exosomes secreted from various types of cells, making it difficult to selectively isolate exosomes secreted by specific cells.
A research group led by Professor Keisuke Goda of the Graduate School of Science, the University of Tokyo (and Distinguished Professor at the SiRIUS Institute of Medical Research, Tohoku University), has developed a new technique that chemically modifies the surface of exosomes/extracellular vesicles with rare earth (lanthanide) ions, thereby increasing homotypic targeting, the selective binding of exosomes to cells of the same type, by more than 25-fold. The results were published in Nature Biomedical Engineering.
The natural ability of cells to recognize and capture their own small extracellular vesicles is enhanced with lanthanide ions. The engineered vesicles are captured much faster by cells of the same type, even when many vesicles from other cell types are present.
Provided by the University of Tokyo
The research group focused on homotypic targeting, the inherent ability of cells to recognize and bind to cells of the same type. Cancer cells have a large amount of sialic acid on their surface, which is involved in malignancy and metastasis. The group leveraged this property and modified the surface of exosomes with rare earth ions such as europium and terbium showing strong affinity to sialic acid. This resulted in a 25-fold increase in the binding of exosomes to the same type of cells compared to the unmodified control, as well as a significant reduction in the time required to capture the target exosomes. They named this phenomenon "super homotypic targeting."
Using super homotypic targeting, they established two ultra-high-sensitivity liquid biopsy approaches. One of the approaches uses cells to detect specific exosomes. By using a cancer cell line as the capturing tool, they selectively captured the cancer-derived exosomes from a serum sample containing numerous different exosomes. The approach could detect target exosomes contained as low as a few dozens of exosomes per milliliter of serum.
The other approach uses exosomes to detect specific cells. By binding surface-modified exosomes derived from cancer cell lines to cancer cells (circulating tumor cells) in blood samples and boosting their signals by approximately 10,000-fold, the approach could detect a single cancer cell contained in nearly 20 milliliters of blood. The technique was validated using practical samples. They confirmed that the amounts of cancer-derived exosomes and cancer cells in blood samples were significantly higher in mice transplanted with triple-negative breast cancer than in healthy mice and that their amounts increased with tumor progression and decreased by administration of an anticancer drug. Furthermore, the technique could clearly distinguish between the blood samples of patients (n=13) and healthy individuals (n=13), demonstrating its effectiveness even under conditions reflecting real clinical complexity.
In addition to early cancer diagnosis and recurrence monitoring, the technique is expected to have applications in a wide range of fields, including drug delivery, tissue regeneration and immunotherapy.
Journal Information
Publication: Nature Biomedical Engineering
Title: Super homotypic targeting by surface engineering of extracellular vesicles
DOI: 10.1038/s41551-026-01743-2
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.