Uptake and subcellular distribution of radiolabeled polymersomes for radiotherapy

Polymersomes have the potential to solve the recoil problem and to be applied in targeted alpha radionuclide therapy. In this study, we investigated the cellular uptake, post uptake processing and intracellular localization of polymersomes. We found that altering polymersome size and concentration affects the initial uptake and overall uptake capacity. In addition, uptake reached different plateaus between various cell lines and mitotic cells show increased uptake. Live cell microscopy showed polymersomes entered cells and were transported along microtubules in a fast and dynamic way. Evidence for endocytic uptake of polymersomes was obtained from co-localization experiments using endocytic pathway components. Finally, we show the intracellular distribution of polymersomes in 3-D and DNA damage inducing capabilities of 213Bi labeled polymersomes. We conclude that polymersome size and concentration as well as different cell types affect the intracellular uptake. In addition, we elucidated the precise uptake mechanism, geometrical distribution and the extent of DNA damage induction of radiolabelled polymersomes. Moreover, we present advanced assays to investigate uptake characteristics in great detail, a necessity for optimization of polymersomes or other nano-carriers.

ROOBOL Sj;  HARTJES Ta;  SLOTMAN Ja;  DE KRUIJFF R. M.;  TORRELO VILLA G;  ABRAHAM Tsion E.;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  KANAAR R;  VAN GENT D;  HOUTSMULLER Ab;  DENKOVA A.G.;  VAN ROYEN Me;  ESSERS J; 

2020-01-17

Ivyspring International Publishers

JRC116649

2206-7418 (online),   

https://publications.jrc.ec.europa.eu/repository/handle/JRC116649,   

10.7150/ntno.37080 (online),