Innovative Translational Approach for the Treatment of Glioblastoma Multiforme

Abstract

Glioblastoma multiforme (GBM) is the primary malignant and most devastating form of tumor in the central nervous system (CNS). Among all CNS cancers, GBM is a rare grade IV astrocytoma with the worst prognosis initiated by metastasis in the supratentorial region of the brain. Current options for the treatment include surgery, radiation therapy, and chemotherapy, where each treatment has its own limitations. In general, chemotherapy is a widely used non-invasive technique. However, the active pharmaceutical ingredient is usually hydrophobic and thus poorly water-soluble, which hampers clinical implications. In the present thesis, we have used a novel combination of drugs with various nanocarriers to design an efficient water-dispersible drug delivery system. The nanoparticles explored are dendrimer-modified nanoparticles such as nanodiamond (ND), iron oxide, and graphene oxide (GO). The dendrimers used are poly(amidoamine) (PAMAM) and PEG-amine (PEG) with their individual desired specific roles. Previous studies have shown that such nanocarriers hold the potential to cross the blood-brain barrier (BBB), which is prudential for GBM treatment. Nanodrug formulations loaded with drugs not only assisted in water dispersibility but also improved cellular permeability, and drug efficacy at a low dose significantly reduced cell survival. The drug molecules are chosen alone or in combination to target various receptors affecting various cellular pathways, which plays a crucial role in GBM proliferation. Such drug delivery systems are increasingly being assessed as potential candidates for cancer therapeutics and hold great promise in overcoming the side effects of traditional chemotherapeutics, raising the overall practical value.