Upconversion nanoparticles for super-resolution quantification of single small extracellular vesicles

eLight - Tập 2 - Trang 1-12 - 2022
Guan Huang1, Yongtao Liu1,2, Dejiang Wang1, Ying Zhu1,3,4, Shihui Wen1, Juanfang Ruan5, Dayong Jin1,6,7
1Institute for Biomedical Materials and Devices (IBMD), Faculty of Science, University of Technology Sydney, Sydney, Australia
2Smart Computational Imaging Laboratory (SCILab), School of Electronic and Optical Engineering, Nanjing University of Science and Technology, Nanjing, China
3School of Biomedical Engineering, Faculty of Engineering and Information Technology, University of Technology Sydney, Sydney, Australia
4School of Clinical Medicine, Faculty of Medicine & Health, UNSW Sydney, Sydney, Australia
5Electron Microscope Unit, UNSW Sydney, Sydney, Australia
6ARC Research Hub for Integrated Device for End-User Analysis at Low Levels, Faculty of Science, University of Technology Sydney, Sydney, Australia
7UTS-SUStech Joint Research Centre for Biomedical Materials and Devices, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, China

Tóm tắt

Although small EVs (sEVs) have been used widely as biomarkers in disease diagnosis, their heterogeneity at single EV level has rarely been revealed. This is because high-resolution characterization of sEV presents a major challenge, as their sizes are below the optical diffraction limit. Here, we report that upconversion nanoparticles (UCNPs) can be used for super-resolution profiling the molecular heterogeneity of sEVs. We show that Er3+-doped UCNPs has better brightness and Tm3+-doped UCNPs resulting in better resolution beyond diffraction limit. Through an orthogonal experimental design, the specific targeting of UCNPs to the tumour epitope on single EV has been cross validated, resulting in the Pearson’s R-value of 0.83 for large EVs and ~ 65% co-localization double-positive spots for sEVs. Furthermore, super-resolution nanoscopy can distinguish adjacent UCNPs on single sEV with a resolution of as high as 41.9 nm. When decreasing the size of UCNPs from 40 to 27 nm and 18 nm, we observed that the maximum UCNPs number on single sEV increased from 3 to 9 and 21, respectively. This work suggests the great potentials of UCNPs approach “digitally” quantify the surface antigens on single EVs, therefore providing a solution to monitor the EV heterogeneity changes along with the tumour progression progress.

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