Researchers including those from the University of Tokyo found a way to optimize how cells bind to small packages they release called extracellular vesicles. By coating the vesicles with metal ions, they made cells and their corresponding vesicles stick together more strongly than they would naturally. This reduced the time needed for cells to capture their own vesicles, even in mixtures containing billions of other vesicles. The team demonstrated an application of this by improving two kinds of blood tests for cancer cells, and it could have downstream applications in drug delivery, rejuvenation and more.
Anyone afflicted with cancer will often face a long and difficult journey. The early stages of any medical intervention will necessarily include a biopsy, tissue sample collection, such as a liquid biopsy which uses a blood sample. These aren’t perfect, but medical researchers are trying to improve them, with one such method being how to amplify the signals indicating cancer cells. This should be possible as all cells release tiny telltale particles known as extracellular vesicles. Professor Keisuke Goda from the Department of Chemistry at the University of Tokyo and his team members found a way to engineer extracellular vesicles in a way never seen before which could improve liquid biopsies and aid in some other medical and research applications..
“Each extracellular vesicle is only about a thousandth the width of a human hair and carries a tiny sample of material from the cell that made it like a little molecular ‘message in a bottle.’ Cancer cells release these packages too but finding them in blood is like searching for a few specific grains of sand on a beach,” said Assistant Professor Tianben Ding from the Department of Chemistry. “So, we developed a simple way to make both the packages and the cancer cells much easier to find. By coating the packages with tiny amounts of lanthanide metals, we made matching packages and cells stick together over 25 times more strongly. This provides a versatile platform that can improve how engineered extracellular vesicles interact with their target cells, enabling applications ranging from cancer detection to targeted drug delivery and rejuvenation.”
The researchers named the enhanced effect super homotypic targeting because it dramatically amplifies cells’ natural tendency to recognize others of the same type. Rather than creating a single new diagnostic test, the researchers see the technique as a platform for engineering extracellular vesicles to perform different tasks. For the purpose of this study, they focused on sialic acid, a sugar abundantly present on the surface of many cancer cells. Lanthanide ions such as europium and terbium bind strongly to this sugar, allowing engineered extracellular vesicles to form much stronger interactions with cells of the same type.
“By decorating extracellular vesicle surfaces with these ions, we effectively added many extra ‘grips,’ so extracellular vesicles and cells of the same lineage bound to one another more strongly, and a capture process that used to take more than two days finished in about three hours,” said Ding. “Using a cell’s own vesicles, upgraded with metal ions, as a way to boost recognition between same-type cells is a new concept. We’re thrilled that we could turn it into two working diagnostic tools with record-breaking sensitivity, rather than just making a single small improvement.”
The team demonstrated these techniques and their results first in cell cultures, then in mice test subjects, and finally in human triple-negative breast cancer samples. The tools referred to above serve as a detector that captures a cancer’s extracellular vesicles and as a probe made of an extracellular vesicle that finds cancer cells to amplify their signals. The latter effectively boosts the signal indicating presence of a cancer cell by a factor of 10,000. This makes even a single cell in a relatively large sample possible to find with a set of typical lab equipment, achieving extreme sensitivity and extreme selectivity at the same time.
“The biggest challenge was achieving both extreme sensitivity and extreme selectivity at the same time. Cancer signals in blood are hard to detect with just a few dozen extracellular vesicles in a milliliter of serum, or a single cancer cell among billions of healthy blood cells,” said Ding. “Making a test more sensitive means detecting more false signals too, so we carefully optimized the chemistry to strengthen the binding between matching cells and extracellular vesicles while minimizing unwanted interactions. We also developed a way to amplify the signal around 10,000 times, making even a single cancer cell detectable. Seeing this work consistently in cultured cells, mice and patient samples made all the effort worthwhile.”
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Journal:
Huai-Song Wang, Tianben Ding, Yuhong Liu, Fabio Lisi, Yuqi Zhou, Yaqi Zhao, Xin-Yuan Hu, ZiWei Yang, Jing-Lian Su, Mika Hayashi, Natsumi Tiffany Ishii, Hiroki Matsumura, Anel Umirbaeva, Hongwei Guo, Yin-Yu Yan, Fu-Han Gao, Jia-Jing Li, Yasutaka Kitahama, Petra Paiè, Ayumi Taguchi, Kenbun Sone, Yuka Inoue, Takayuki Ueno, Abdullah N. Alodhayb, Nao Nitta, Masako Nishikawa, Yutaka Yatomi, Hiroyuki Matsumura, Ya Ding, Masahiro Sonoshita, Dino Di Carlo, Shiro Suetsugu, and Keisuke Goda. “Super homotypic targeting by surface engineering of extracellular vesicles”, Nature Biomedical Engineering, DOI: 10.1038/s41551-026-01743-2, https://www.nature.com/articles/s41551-026-01743-2
Funding:
JSPS: JPJSCCA20190007, JP19H05633, JP20H00317, JP21H05047, JP20KK0341, JP20H03252, JP24K17800, JPMJST2115, JPMJCR1863, JPMJCR24B3, JPMJAP2316.
AMED: 22ak0101163h0002.
MEXT Quantum Leap Flagship Program: JPMXS0120330644.
XPRIZE Foundation.
KAKETSUKEN.
White Rock Foundation.
G-7 Scholarship Foundation.
China Scholarship Council: 202107060015.
Deanship of Scientific Research at King Saud University: MbSC2030.
Mohammed bin Salman Center for Future Science and Technology for Saudi-Japan Vision 2030.
Cell Aging Control Endowed Chair at the University of Tokyo.
Useful links:
Goda Lab - https://goda.chem.s.u-tokyo.ac.jp/
Department of Chemistry - https://www.chem.s.u-tokyo.ac.jp/wp/en
Graduate School of Science - https://www.s.u-tokyo.ac.jp/en/
Research Contact:
Professor Goda Keisuke
Department of Chemistry, The University of Tokyo,
7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
goda@chem.s.u-tokyo.ac.jp
Press contact:
Mr. Rohan Mehra
Strategic Communications Group, The University of Tokyo,
7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan
press-releases.adm@gs.mail.u-tokyo.ac.jp
About The University of Tokyo:
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Nature Biomedical Engineering
Experimental study
Cells
Super homotypic targeting by surface engineering of extracellular vesicles
23-Jul-2026