Temozolomide Nanoparticles for Targeted Glioblastoma Therapy

Abstract

Glioblastoma (GBM) is a deadly and debilitating brain tumor with an abysmal prognosis. The standard therapy for GBM is surgery followed by radiation and chemotherapy with Temozolomide (TMZ). Treatment of GBMs remains a challenge, largely because of the fast degradation of TMZ, the inability to deliver an effective dose of TMZ to tumors, and a lack of target specificity that may cause systemic toxicity. Here, we present a simple method for synthesizing a nanoparticle-based carrier that can protect TMZ from rapid degradation in physiological solutions and can specifically deliver them to GBM cells through the mediation of a tumor-targeting peptide chlorotoxin (CTX). Our nanoparticle, namely NP-TMZ-CTX, had a hydrodynamic size of <100 nm, exhibited sustained stability in cell culture media for up to 2 weeks, and could accommodate stable drug loading. TMZ bound to nanoparticles showed a much higher stability at physiological pH, with a half-life 7-fold greater than that of free TMZ. NP-TMZ-CTX was able to target GBM cells and achieved 2-6-fold higher uptake and a 50-90% reduction of IC50 72 h post-treatment as compared to nontargeted NP-TMZ. NP-TMZ-CTX showed great promise in its ability to deliver a large therapeutic dose of TMZ to GBM cells and could serve as a template for targeted delivery of other therapeutics.