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Nanotheranostics. 2020 Jan 1;4(1):14-25. doi: 10.7150/ntno.37080. eCollection 2020.

Uptake and subcellular distribution of radiolabeled polymersomes for radiotherapy.

Author information

1
Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
2
Oncode Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
3
Department of Radiology & Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
4
Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
5
Optical Imaging Centre (OIC), Erasmus University Medical Center, Rotterdam, The Netherlands.
6
Department of Radiation Science and Technology, Delft University of Technology, Delft, The Netherlands.
7
European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, Karlsruhe, Germany.
8
Cancer Treatment Screening Facility (CTSF), Erasmus University Medical Center, Rotterdam, The Netherlands.
9
Department of Radiation Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
10
Department of Vascular Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.

Abstract

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 of 213Bi 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.

KEYWORDS:

Polymersomes; live cell confocal microscopy; nano-carriers; radionuclide therapy; uptake

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

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