Uptake and subcellular distribution of radiolabeled polymersomes for radiotherapy

Uptake and subcellular distribution of radiolabeled polymersomes for radiotherapy

Roobol, Stefan J. (Erasmus MC)
Hartjes, Thomas A. (Erasmus MC)
Slotman, Johan A. (Erasmus MC)
de Kruijff, R.M. (TU Delft RST/Applied Radiation & Isotopes)
Kanaar, R. (Erasmus MC)
Houtsmuller, A.B. (Erasmus MC)
Denkova, A.G. (TU Delft RST/Applied Radiation & Isotopes)
van Royen, M.E. (Erasmus MC)
Essers, J. (Erasmus MC)

2020

Polymersomes have the potential to be applied in targeted alpha radionuclide therapy, while in addition preventing release of recoiling daughter isotopes. In this study, we investigated the cellular uptake, post uptake processing and intracellular localization of polymersomes. Methods: High-content microscopy was used to validate polymersome uptake kinetics. Confocal (live cell) microscopy was used to elucidate the uptake mechanism and DNA damage induction. Intracellular distribution of polymersomes in 3-D was determined using super-resolution microscopy. Results: We found that altering polymersome size and concentration affects the initial uptake and overall uptake capacity; uptake efficiency and eventual plateau levels varied between cell lines; and mitotic cells show increased uptake. Intracellular polymersomes were transported along microtubules in a fast and dynamic manner. Endocytic uptake of polymersomes was evidenced through co-localization with endocytic pathway components. Finally, we show the intracellular distribution of polymersomes in 3-D and DNA damage inducing capabilities of²¹³Bi labeled polymersomes. Conclusion: Polymersome size and concentration affect the uptake efficiency, which also varies for different cell types. In addition, we present advanced assays to investigate uptake characteristics in detail, a necessity for optimization of nano-carriers. Moreover, by elucidating the uptake mechanism, as well as uptake extent and geometrical distribution of radiolabeled polymersomes we provide insight on how to improve polymersome design.

Live cell confocal microscopy
Nano-carriers
Polymersomes
Radionuclide therapy
Uptake

http://resolver.tudelft.nl/uuid:d3a5e9cb-ab2c-43f6-b278-071b9086e7b6

https://doi.org/10.7150/ntno.37080

Nanotheranostics, 4 (1), 14-25

Institutional Repository

journal article

© 2020 Stefan J. Roobol, Thomas A. Hartjes, Johan A. Slotman, R.M. de Kruijff, R. Kanaar, A.B. Houtsmuller, A.G. Denkova, M.E. van Royen, J. Essers