Super homotypic targeting by surface engineering of extracellular vesicles
Abstract Homotypic targeting is the inherent ability of cells to preferentially interact with cells of the same type, a phenomenon seen in cell adhesion, tissue formation and immune responses. However, its potential remains underexploited. Here we report a strategy to substantially enhance homotypic targeting through extracellular vesicles secreted by cells. By engineering the surface of small extracellular vesicles (sEVs) with lanthanides, we amplify specific cell–sEV interactions by more than 25-fold, enabling the selective capture of sEVs by cells of the same lineage even in the presence of excess off-target sEVs. We term this effect ‘super homotypic targeting’. Super homotypic targeting provides a means to distinguish sEVs of different origins within highly heterogeneous sEV populations and enables two applications: using cells to detect specific sEVs and using sEVs to detect specific cells, specifically demonstrated here in the context of cancer detection from blood samples. Super homotypic targeting could hold potential for diagnostics, immunotherapy, drug delivery, rejuvenation and tissue engineering.
Authors
- Natsumi Tiffany Ishii (ORCID: https://orcid.org/0000-0002-8174-9309)
- Keisuke Goda (ORCID: https://orcid.org/0000-0001-6302-6038)
- Tianben Ding (ORCID: https://orcid.org/0000-0003-0710-2344)
- Mika Hayashi (ORCID: https://orcid.org/0000-0002-3917-1400)
- Shiro Suetsugu (ORCID: https://orcid.org/0000-0002-4612-0628)
- Abdullah N. Alodhayb (ORCID: https://orcid.org/0000-0003-0202-8712)
- Hiroyuki Matsumura (ORCID: https://orcid.org/0000-0003-2572-6572)
- Masako Nishikawa (ORCID: https://orcid.org/0000-0002-3840-767X)
- Ya Ding (ORCID: https://orcid.org/0000-0001-6214-5641)
- Nao Nitta (ORCID: https://orcid.org/0000-0002-9093-9016)
- Petra Paiè (ORCID: https://orcid.org/0000-0002-6575-1986)
- Ayumi Taguchi (ORCID: https://orcid.org/0000-0002-5491-3871)
- Masahiro Sonoshita (ORCID: https://orcid.org/0000-0003-2890-336X)
- Huai‐Song Wang
- Zi-Wei Yang
- Fabio Lisi (ORCID: https://orcid.org/0000-0003-3597-596X)
- Hiroki Matsumura (ORCID: https://orcid.org/0000-0003-3638-6956)
- Yasutaka Kitahama (ORCID: https://orcid.org/0000-0002-6447-2774)
- Yutaka Yatomi (ORCID: https://orcid.org/0000-0003-1719-4297)
- Takayuki Ueno (ORCID: https://orcid.org/0000-0002-9080-9377)
- Kenbun Sone (ORCID: https://orcid.org/0000-0002-7218-6401)
- Dino Di Carlo (ORCID: https://orcid.org/0000-0003-3942-4284)
- Anel Umirbaeva
- Yuhong Liu (ORCID: https://orcid.org/0000-0001-5278-7333)
- Hongwei Guo (ORCID: https://orcid.org/0000-0002-1361-8083)
- Fu-Han Gao
- Yaqi Zhao (ORCID: https://orcid.org/0000-0002-5550-9483)
- Yi Zhou (ORCID: https://orcid.org/0000-0001-9610-4370)
- Xinyuan Hu (ORCID: https://orcid.org/0000-0002-7443-1474)
- Yin-Yu Yan
- Jing-Lian Su
- Yuka Inoue
- Jia-Jing Li
Institutions
- Huaqiao University (CN)
- California NanoSystems Institute (US)
- University of California, Los Angeles (US)
- China Pharmaceutical University (CN)
- Tohoku University (JP)
- Hokkaido University (JP)
- Japan Society for the Promotion of Science (JP)
- King Saud University (SA)
- CYBO (Japan) (JP)
- The Cancer Institute Hospital (JP)
- Japanese Foundation For Cancer Research (JP)
- Nazarbayev University (KZ)
- The University of Tokyo (JP)
- Nara Institute of Science and Technology (JP)
- Politecnico di Milano (IT)
Publication Details
- Journal
- Nature Biomedical Engineering
- Published
- 2026-07-22
- DOI
- https://doi.org/10.1038/s41551-026-01743-2
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00