Evaluation of chloroaluminium phthalocyanine-loaded magnetic nanoemulsion as drug delivery device to treat glioblastoma using hyperthermia and photodynamic therapy

Introduction: Brain tumors known as glioma are the most common neoplasms found in the central nervous system of adults. In a brain cancer tumor cancer stem cells (CSCs) represent a small fraction of the total cancer cell... [ view full abstract ]

Introduction: Brain tumors known as glioma are the most common neoplasms found in the central nervous system of adults. In a brain cancer tumor cancer stem cells (CSCs) represent a small fraction of the total cancer cell population. Studies have suggested similarities of CD133+ CSC with the proneural subtype and of CD133 CSC with the mesenchymal subtype. Methods: We developed two samples magnetic nanoemulsions (MNEs) loaded with magnetic nanoparticles (MNPs) plus photoactivated drugs, chloroaluminium phthalocyanine (ClAlPc), (0.15×1016 or 1.50×1016 MNP/mL), were obtained through a spontaneous emulsification process based on oil-in-water mixtures. All the cell lines (human mesenchymal stem cells derived from bone marrow - BM-MSC and the human glioma - U87MG and T98G) were cultived in alpha-MEM, DMEM-low and 10% fetal bovine serum at 37 ºC and 5% CO2, respectively. The AC magnetic field during the hyperthermia (HPT) studies operates at 1 MHz with 40 Oe magnetic field amplitude. Photodynamic therapy (PDT) protocol used a typical diode laser set at 670 nm and operates with 100, 200, and 700 mJ/cm2 fluency. For different treatments the cell viability was assessed by the MTT test. Results and Discussion: Particle size analysis showed that all colloidal formulations produced in the present study and containing ClAlPc were on the nanoscale size, with typical mean diameter around 200 nm and size distribution value of 0.25. Cytotoxicity assay was conducted with the MNE/ClAlPc samples at the two distinct MNP concentrations while keeping fixed the ClAlPc concentration (0.5 µmol/L). Synergism of the combined HPT and PDT treatments, revealing an increase of up to 60-70% in cell death. Conclusion: From the present study we found that the HPT treatment reduces the cell viability in about 15%, regardless the magnetic nanoparticle content within the MNE. However, a superior reduction in cell viability of about 70% was found while combining the HPT and PDT treatments. Moreover, confocal microscopy images clearly indicated the cytoplasm localization and active site of the as-prepared drug delivery device. Therefore, we envisage that the combined treatment of HPT and PDT represents a promising paradigm for brain cancer intervention, such as glioblastoma.