Article 58

3D spheroid culture; microwell array; immunohistochemistry; pathology; glioblastoma; breast adenocarcinoma

Mesostructured silica, such as MCM-41 and SBA-15 and aluminosilicates have demonstrated good biocompatibility and are used as nanosized drug delivery systems (DDSs). Doping with aluminium modulates their physico-chemical properties. This study aimed to assess the metabolic impact of the 24 h or 48 h incubation of NIH3T3 murine fibroblastic cells with three categories of aluminium-doped MCM-41 and SBA-15 used as DDSs for the cytotoxic irinotecan. After 24 h, unloaded Al-doped DDSs at 90 μg/mL presented no toxic effects. Irinotecan release from DDSs followed a Fickian diffusion with various release profiles. Higher Al content led to higher residual drug amounts, while larger pore sizes resulted in faster desorption of irinotecan. Irinotecan loaded onto Al-doped DDSs decreased cell viability compared to irinotecan in solution. The MCM-based carriers demonstrated greater effectiveness in delivering irinotecan than SBA-based DDSs. The 48 h discontinuous exposure to irinotecan-loaded DDSs exhibited similar cytotoxicity to continuous exposure, suggesting a saturation of DDSs cellular uptake. Confocal microscopy revealed that DDSs were embedded in the cell membranes, supporting the hypothesis of an endocytosis-driven uptake. Our results showed that mesoporous aluminosilicates can augment intracellular irinotecan delivery as a Trojan horse.