Enhanced accumulation of curcumin and temozolomide loaded magnetic nanoparticles executes profound cytotoxic effect in glioblastoma spheroid model

Glioblastomas (GBMs) are highly lethal primary brain tumours. Treatment of these malignant gliomas remains ineffective as these are extremely resistant to chemotherapeutic applications. Furthermore, combination therapy for cancer treatment is becoming more popular because it generates synergistic anticancer effects, by reducing individual drug-related toxicity and associated side effects. Currently, magnetic nanoparticles (MNPs) based drug delivery system has attracted much more attention owing to its intrinsic magnetic properties and drug loading capacity. In the present study, MNPs based drug delivery approach for co-delivering of potent chemotherapeutic drugs such as Curcumin (herbal drug) and Temozolomide (DNA methylating agent) has been implemented. The dual drug loaded MNPs formulations were evaluated in two-dimensional (2-D) monolayer culture and three-dimensional (3-D) tumour spheroid culture of T-98G cells for understanding the therapeutic discrepancy. The dual drug loaded MNPs formulations demonstrated higher cytotoxic effect than single drug loaded MNPs formulations as compared to their corresponding native drugs in 2-D and 3-D culture. The combination index (CI) analysis revealed synergistic mode of action of dual drug loaded MNPs formulations, which was further confirmed by cell death induction assay mediated by acridine orange (AO)/propidium iodide (PI) staining, illustrating higher efficacy of the formulation towards GBM therapy.

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