The therapeutic potential of polymersomes loaded with 225Ac evaluated in 2D and 3D in vitro glioma models

Alpha emitters have great potential in targeted tumour therapy, especially in destroying micrometastases, due to their high linear energy transfer (LET). To prevent toxicity caused by recoiled daughter atoms in healthy tissue, alpha emitters like 225Ac can be encapsulated in polymeric nanocarriers (polymersomes), which are capable of retaining the daughter atoms to a large degree. In the translation to a (pre-)clinical setting, it is essential to understand the interaction of these vesicles with tumour cells. As multicellular tumour spheroids mimic a tumour microenvironment more closely than a two-dimensional cellular monolayer, in this study the uptake and distribution of the polymersomes has been determined in U87 human glioma spheroids. We have found that polymersomes have distributed themselves throughout the spheroid after 4 days, at all polymersome diameters (100 to 800 nm). Considering the long half-life of 225Ac (9.9 d) [1], this allows for irradiation and destruction of the entire spheroid within a few days. A decrease in spheroidal growth was observed upon the addition of only 0.1 kBq 225Ac, an effect which was more pronounced for the 225Ac in polymersomes than when only coupled to DTPA. At higher activities (5 kBq), the spheroids were found to be destroyed completely within a few days. We demonstrate that polymersomes loaded with very low 225Ac activities inhibited the growth of spheroids, making them very promising candidates for future in vivo testing.

DE KRUIJFF R. M.;  VAN DER MEER A;  WINDMEIJER C.A.A.;  KOUWENBERG J;  MORGENSTERN Alfred;  BRUCHERTSEIFER Frank;  SMINIA P;  DENKOVA A.G.; 

2018-05-03

ELSEVIER SCIENCE BV

JRC108510

0939-6411,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC108510,   

10.1016/j.ejpb.2018.02.008,