Polymeric nanocarriers for the delivery of radiosensitizers to brain tumours

Gabriel Becerril Aragon, Robin de Kruijff, Astrid Van der Meer, Ana Gasol, A G Denkova, P Sminia

Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review


Abstract. The amid MEK162 (Binimetinib®, Array Biopharma) free or uploaded onto polybutadiene-b-poly(ethylene oxide) polymersomes (PB-b-PEO PS) inhibited MAPK/ERK signalling pathway and enhanced radiation induced damage in glioma U87-spheroid cultures as established by individual spheroid growth, imaged by transmission microscopy, and spheroid volume, measured with the imaging software Scratch Assay 6.2 (DCILabs).
However, immune-blot measurements of the levels of the target of MEK162, the protein pERK, disclosed that the inhibition caused by free MEK162 was more durable than that caused by MEK162 loaded onto PB-b-PEO PS. The levels of γH2AX showed that the enhancement of radio-induced DNA damage was also larger in the spheroid cultures treated with free MEK162. As a means to elucidate whether MEK162 leaks from PB-b-PEO PS, we collected time-fractions of the outflow from loaded-PS suspended in solid phase extraction columns, vacuum dried and solubilised them, and then determined their MEK162-content by liquid chromatography tandem mass spectrometry. The dynamics of the leakage of MEK162 from PB-b-PEO PS in suspension fitted to Higuchi model of diffusion from insoluble matrices as confirmed by the correlation coefficient R2 of the experimental data plotted as square root function of time. Nevertheless, the small magnitude of MEK162 leakage in the experimental period (220 minutes) represented 1,79 ± 0,21% of its initial content in the suspension, what confirms that PB-b-PEO PS are prospective nanocarriers for further anti-cancer research.
Original languageEnglish
Title of host publicationRadiobiology: Current Issues. Proceedings of the International Scientific Conference
Number of pages4
Publication statusPublished - 27 Sep 2018

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