Synthesis and Functionalisation of Superparamagnetic Nano-Rods towards the Treatment of Glioblastoma Brain Tumours

Abstract

The complete removal of glioblastoma brain tumours is impossible to achieve by surgery alone due to the complex finger-like tentacle structure of the tumour cells and their migration away from the bulk of the tumour at the time of surgery; furthermore, despite aggressive chemotherapy and radiotherapy treatments following surgery, tumour cells continue to grow, leading to the death of patients within 15 months after diagnosis. The naturally occurring carnosine dipeptide has previously demonstrated activity against in vitro cultured glioblastoma cells; however, at natural physiological concentrations, its activity is too low to have a significant effect. Towards realising the full oncological potential of carnosine, the dipeptide was embedded within an externally triggered carrier, comprising a novel nano rod-shaped superparamagnetic iron oxide nanoparticle (ca. 86 × 19 × 11 nm) capped with a branched polyethyleneimine, which released the therapeutic agent in the presence of an external magnetic field. The new nano-carrier was characterized using electron microscopy, dynamic light scattering, elemental analysis, and magnetic resonance imaging techniques. In addition to cytotoxicity studies, the carnosine carrier’s effectiveness as a treatment for glioblastoma was screened in vitro using the U87 human glioblastoma astrocytoma cell line. The labile carnosine (100 mM) suppresses both the U87 cells’ proliferation and mobility over 48 h, resulting in significant reduction in migration and potential metastasis. Carnosine was found to be fully released from the carrier using only mild hyperthermia conditions (40 °C), facilitating an achievable clinical application of the slow, sustained-release treatment of glioblastoma brain tumours that demonstrates potential to inhibit post-surgery metastasis with the added benefit of non-invasive monitoring via MRI.

Ferrimagnetic Large Single Domain Iron Oxide Nanoparticles for Hyperthermia Applications

“…Magnetic iron oxide nanoparticles (MNPs) are of great interest for hyperthermia applications as a therapeutic approach mainly for tumor diseases [ 1 , 2 , 3 , 4 , 5 ], utilizing their unique feature of heat generation when placed in an external alternating magnetic field caused by the reorientation of the magnetic moment of the particle. In this medical setting, strict limits have to be met concerning the applied magnetic field to ensure patient safety.…”

Modernistic and Emerging Developments of Nanotechnology in Glioblastoma-Targeted Theranostic Applications

“…The mild hyperthermia (ca. 40 • C) produced by the magnetic oscillations of nanorods can help in the controlled release of carnosine against glioblastoma [98]. Here, we can praise the diagnostic performance of the SPIONs due to their extreme T 2 relaxation that can improve the quality of the contrast of the images [99].…”

Nanotherapeutics Overcoming the Blood-Brain Barrier for Glioblastoma Treatment

“…Besides monoclonal antibodies, peptides have been widely used in the prevention, diagnosis, and treatment of tumors and other diseases, for their lower price, easy to mass production, low immunogenicity, and stronger permeability in tissues ( Habra et al, 2021 ). The human mesenchymal-epithelial conversion factor (MET) proto-oncogene is located on chromosome 7q31.…”