Uptake and subcellular distribution of radiolabeled polymersomes for radiotherapy
| Autor: | Guzman Torrelo, Tsion E Abraham, Frank Bruchertseifer, Robin M. de Kruijff, Dik C. van Gent, Martin E. van Royen, Adriaan B Houtsmuller, Thomas A Hartjes, Roland Kanaar, Antonia G. Denkova, Jeroen Essers, Alfred Morgenstern, Johan A. Slotman, Stefan J. Roobol |
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| Přispěvatelé: | Molecular Genetics, Radiology & Nuclear Medicine, Pathology, Radiotherapy, Surgery |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Polymersomes
Polymers Nano-carriers DNA damage Cell Endocytic cycle Biomedical Engineering Uptake Medicine (miscellaneous) 02 engineering and technology Radionuclide therapy Cell Line Mice 03 medical and health sciences Cell Line Tumor medicine Animals Humans Distribution (pharmacology) Organic Chemicals Pharmacology Toxicology and Pharmaceutics (miscellaneous) 030304 developmental biology Radioisotopes Drug Carriers 0303 health sciences Microscopy Confocal Radiotherapy Live cell confocal microscopy Chemistry Membranes Artificial 021001 nanoscience & nanotechnology Endocytosis medicine.anatomical_structure Cell culture Polymersome Biophysics Nanoparticles 0210 nano-technology Bismuth Intracellular Research Paper Biotechnology |
| Zdroj: | Nanotheranostics, 4, 14-25. Ivyspring International Publishers Nanotheranostics, 4(1) Nanotheranostics |
| ISSN: | 2206-7418 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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