Label-free characterization and real-time monitoring of cell uptake of extracellular vesicles

Annika Koponen, Erja Kerkelä, Tatu Rojalin, Elisa Lázaro-Ibáñez, Teemu Suutari, Heikki O. Saari, Pia Siljander, Marjo Yliperttula, Saara Laitinen, Tapani Viitala*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

17 Citations (Scopus)


Extracellular vesicles (EVs) have the ability to function as molecular vehicles and could therefore be harnessed to deliver drugs to target cells in diseases such as cancer. The composition of EVs determines their function as well as their interactions with cells, which consequently affects the cell uptake efficacy of EVs. In this study, we present two novel label-free approaches for studying EVs; characterization of EV composition by time-gated surface-enhanced Raman spectroscopy (TG-SERS) and monitoring the kinetics and amount of cellular uptake of EVs by surface plasmon resonance (SPR) in real-time. Using these methods, we characterized the most abundant EVs of human blood, red blood cell (RBC)- and platelet (PLT)-derived EVs and studied their interactions with prostate cancer cells. Complementary studies were performed with nanoparticle tracking analysis for concentration and size determinations of EVs, zeta potential measurements for surface charge analysis, and fluorophore-based confocal imaging and flow cytometry to confirm EV uptake. Our results revealed distinct biochemical features between the studied EVs and demonstrated that PLT-derived EVs were more efficiently internalized by PC-3 cells than RBC-derived EVs. The two novel label-free techniques introduced in this study were found to efficiently complement conventional techniques and paves the way for further use of TG-SERS and SPR in EV studies.

Original languageEnglish
Article number112510
JournalBiosensors and Bioelectronics
Publication statusPublished - 15 Nov 2020
Externally publishedYes
MoE publication typeA1 Journal article-refereed


  • Cell uptake
  • Extracellular vesicles
  • Prostate cancer cells
  • Surface plasmon resonance
  • Time-gated surface-enhanced Raman spectroscopy


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