Abstract
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 language | English |
|---|---|
| Article number | 112510 |
| Journal | Biosensors and Bioelectronics |
| Volume | 168 |
| DOIs | |
| Publication status | Published - 15 Nov 2020 |
| Externally published | Yes |
| MoE publication type | A1 Journal article-refereed |
Funding
The authors thank Viikki Flow Cytometry Core Facility, EV Core Facility and the Light Microscopy Unit, Institute of Biotechnology (all University of Helsinki). Lotta Sankkila, Lotta Andersson and Birgitta Rantala are acknowledged for their excellent technical assistance. Funding: Finnish Funding Agency for Technology/Business Finland (Grant nos. 440211 (AK, MY), 440935 (PS, MY, TV), Salwe GID (SL)), Sigrid Juselius Foundation (TR), Doctoral Programme in Materials Research and Nanoscience (TS), Alfred Kordelin Foundation (EL-I), Emil Aaltonen foundation (HOS), Academy of Finland (Grant nos. 287089 (PS), 294309 (TV, AK)) and Magnus Ehrnrooth Foundation (PS) are gratefully acknowledged. The authors thank Viikki Flow Cytometry Core Facility, EV Core Facility and the Light Microscopy Unit, Institute of Biotechnology (all University of Helsinki). Lotta Sankkila, Lotta Andersson and Birgitta Rantala are acknowledged for their excellent technical assistance. Funding: Finnish Funding Agency for Technology/Business Finland (Grant nos. 440211 (AK, MY), 440935 (PS, MY, TV), Salwe GID (SL)), Sigrid Juselius Foundation (TR), Doctoral Programme in Materials Research and Nanoscience (TS), Alfred Kordelin Foundation (EL-I), Emil Aaltonen foundation (HOS), Academy of Finland (Grant nos. 287089 (PS), 294309 (TV, AK)) and Magnus Ehrnrooth Foundation (PS) are gratefully acknowledged.
Keywords
- Cell uptake
- Extracellular vesicles
- Prostate cancer cells
- Surface plasmon resonance
- Time-gated surface-enhanced Raman spectroscopy