Combined Chemoradionuclide Therapy Using Poly(ε-caprolactone-b-ethylene oxide) Micelles as the Delivery Vehicle

Combination of therapies is a common strategy in cancer treatment. Such combined therapies only have merit provided that there is superior therapeutic outcome with fewer side effects, compared to single therapies. Here, this work explores the possibility to combine chemotherapy with radionuclide therapy using polymeric micelles as a delivery vehicle. For this purpose, this work prepares poly(ε-caprolactone-b-ethylene oxide) (PCL-PEO) micelles and load them simultaneously with paclitaxel (PTX) and ¹⁷⁷Lu(III). This work chooses a 3D tumor spheroid composed of glioblastoma cells (U87) to evaluate the combined treatment. The diffusion of the micelles in the spheroid is investigated by confocal laser scanning microscopy (CLSM) and light-sheet fluorescence microscopy (LSFM). The results show that the micelles are able to penetrate deep into the spheroid within 24 h of incubation and mainly accumulated around or in the lysosomes once in the cell. Subsequently, this work evaluates the cell killing efficiency of the single treatments (PTX or ¹⁷⁷Lu(III)) versus combined treatment (PTX + ¹⁷⁷Lu(III)) by measuring the growth of the spheroids as well as by performing a cell-viability assay. The results indicate that the combined therapy achieves a superior therapeutic outcome with better cell growth inhibition and cell killing efficiency compared to the single treatments.