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

Abstract

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.

Nanomaterials for Molecular Detection and Analysis of Extracellular Vesicles

“…A remarkable recent study by Huang et al extended UCNPs to detect single EVs [ 129 ]. The authors found that while the Er 3+ -doped UCNPs had a better brightness, the Tm 3+ -doped UCNPs had a better resolution beyond the diffraction limit.…”

The development of rare-earth combined Fe-based magnetic nanocomposites for use in biological theranostics

“…25 The 4f electron orbital endows most RE ions with abundant intermediate energy levels for electronic transitions, 26 enabling Ho 3+ , Nd 3+ , Er 3+ , and Tm 3+ to exhibit upconverted luminescence in the range from the UV band to near-infrared light (NIR). 27 The corresponding RE-based upconversion nanoparticles are well known for application in bioimaging, [28][29][30] photothermal therapy (PTT), [31][32][33] photodynamic therapy (PDT), 34,35 drug delivery, 36,37 and other biomedical fields. Interestingly, the unpaired electrons in the 4f layer and spin-orbital coupling also endow Ln 3+ paramagnetic candidates 38 with high magnetic moment and magnetic susceptibility as shown in Fig.…”

Enhanced Photoluminescence of Gd3Al4GaO12: Cr3+ by Energy Transfers from Co-Doped Dy3+

“…Therefore, broad, deep-red lighting devices suitable for plant growth have become the focus [ 10 ]. At present, phosphor-converted light-emitting diodes (pcLEDs) based on blue chips, are among the most effective lighting means [ 11 , 12 , 13 , 14 ].…”