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

Kinana Habra,Robert H. Morris,Stéphanie E. B. McArdle,Gareth W. V. Cave

doi:10.3390/nano11092157

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.

Highlights

Glioblastoma multiforme (GBM) is the most malignant form of glioma and accounts for about 15% of all brain tumours and 60% of primary brain tumours
We describe the synthesis of superparamagnetic iron oxide nano-rods (IONRs) coated with a branched polymer that can be loaded and unloaded with carnosine, using mild hyperthermia as a controlled release carrier that is stable under physiological conditions
TEM, FTIR and powder X-ray diffraction (XRD) studies confirmed that the IONRs were

Summary

Introduction

Glioblastoma multiforme (GBM) is the most malignant form of glioma and accounts for about 15% of all brain tumours and 60% of primary brain tumours. The main contributing factor to the low survival rates is attributed to the persistence of residual malignant cells that have been found to be resistant to chemotherapy and radiotherapy, resulting in rapid recurrence [2]. It is, imperative to look towards new theragnostic approaches to treat this terminal disease [1,3]. In order to mitigate the risk of residual malignant cells post-surgery, real time medical imaging (e.g., MRI) during surgery is emerging as a new tool for surgeons to help reduce recurrence; to optimise this process, a targeted contrast agent is required [4,5,6,7].

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Conclusion