Multifunctional Theranostic Nanoparticles for Brain Tumors

Abstract

Antiangiogenic approaches have been extensively exploited to provide a rationally designed therapy for the treatment of brain cancer. The brain tumor endothelium, with characteristics of high proliferation, high permeability, and high expression of proangiogenic factors (such as vascular endothelial growth factor, VEGF), is a particularly appealing therapeutic target for this strategy. Many antibody drugs, which primarily target the interaction between VEGF and its receptors, have been investigated in clinical trials but have shown only modest effects. Recent research published by Agemy et al.1 has alternatively harnessed a tumor-homing peptide (CGKRK) to specifically deliver multifunctional theranostic nanoparticles composed of iron oxide nanoworm (NW) and mitochondria-targeted cytotoxic peptide D[KLAKLAK]2 to glioblastoma multiforme (GBM) endothelium. Moreover, with the help of a tumor-penetrating peptide (iRGD), the NWs were capable of infiltrating the tumor tissue after extravasation for tumor cell eradication. This strategy was evaluated in lentivirus-induced, transplantable, and orthotopic brain tumor models. Complete tumor ablation was achieved in the first model and significant prolongation of survival was observed in the latter two models, suggesting promise for eventual clinical application.