Galectin inhibitors and nanoparticles as a novel therapeutic strategy for glioblastoma multiforme

Abstract

Over the past two decades, the gold standard of glioblastoma multiforme (GBM) treatment is unchanged and adjunctive therapy has offered little to prolong both quality and quantity of life. To improve pharmacotherapy for GBM, galectins are being studied provided their positive correlation with the malignancy and disease severity. Despite the use of galectin inhibitors and literature displaying the ability of the lectin proteins to decrease tumor burden and decrease mortality within various malignancies, galectin inhibitors have not been studied for GBM therapy. Interestingly, anti-galectin siRNA delivered in nanoparticle capsules, assisting in blood brain barrier penetrance, is well studied for GBM, and has demonstrated a remarkable ability to attenuate both galectin and tumor count. Provided that the two therapies have an analogous anti-galectin effect, it is hypothesized that galectin inhibitors encapsuled within nanoparticles will likely have a similar anti-galectin effect in GBM cells and further correlate to a repressed tumor burden.

Keywords: Galectin-1; galectin inhibitors; glioblastoma; nanoparticles.

Figure 1

Depicts the cyclical nature of galectin-mediated tumor progression. Glioma cells upregulate various galectin isoforms found in the central nervous system. These glycan-binding proteins mediate various oncogenic processes including neuroinflammation, enhanced angiogenesis, apoptosis regulation, autophagy induction, and cancer metabolism. These processes increase glioma mass and metastatic potential which subsequently promotes a vicious tumor-promoting cycle.

Figure 2

Begins by listing various galectin inhibitors tested in clinical trials for non-GBM pathologies. The listed galectin inhibitors, in addition to others not mentioned in the figure, can be added to a specific nanoparticle with or without TMZ. The galectin-inhibitor nanoparticle complex can then be prepared as a solution that can be administered to glioblastoma animal models, such as mice, through intravenous, intranasal, or intracranial routes.