Synthesis of fluorescent organosilica nanoparticles doped with rare-earth metals for the detection of extracellular vesicles by flow cytometry

Extracellular vesicles (EVs) are important players in intercellular communication and active mediators of many diseases (e.g., cardiovascular diseases and cancer). Of the clinical laboratory techniques, only flow cytometry (FCM) may be suitable for routine examination of EVs, however, due to the lack of currently available reference particles for EVs that resembles their light scattering properties, the clinical application of EV-based biomarker analysis is not yet widespread.
The ideal reference particle required to characterize EVs with FCM is in the size range of 50 nm to 500 nm, has a low refractive index, and contains a stable, well-characterized fluorescent label. Hollow organosilica nanoparticles (HOBs) meet the first two criteria, however, their fluorescent labeling has not yet been resolved. In the framework of the present collaboration, we plan to prepare HOBs labeled with fluorescent rare earth metal complexes (e.g., Eu, Gd, Er) by co-condensation of triethoxysilyl-modified chelators and organosilicate precursors.

The designed fluorescent HOBs would be the first to allow simultaneous light scattering and fluorescence-based calibration of FCM-based EV measurements. Besides, the rare earth metal doping of such HOBs would make possible the determination of the absolute particle number concentration of the particles with single particle ICP-MS that we intend to carry out in international collaboration.

Roland Szalay, Zoltán Varga