Targeted Therapy for Glioblastoma: Synergistic Effects of GO/C-TMZ,@, PmAb and Magnetic Hyperthermia

Abstract

This study investigates the therapeutic potential of a nanohybrid structure, GO/C-TMZ@PmAb MNP, for targeted glioblastoma treatment by integrating chemotherapy with magnetic hyperthermia. Characterization of the nanohybrid confirmed successful conjugation of Panitumumab (PmAb) and effective loading of Temozolomide (TMZ), ensuring targeted delivery to glioblastoma cells. In vitro experiments demonstrated enhanced cytotoxicity and a significant increase in late-stage apoptosis in U-87 MG and U-251 MG glioblastoma cell lines, particularly when combined with an alternating magnetic field (AMF), highlighting the synergistic effect of combined therapy. Cellular uptake studies via ICP-OES and fluorescence microscopy revealed maximum uptake at 6 h postincubation. In vivo studies using a subcutaneous U-251 MG tumor model showed substantial inhibition of tumor growth, increased necrosis, and apoptosis rates, as well as reduced EGFRvIII expression in treated groups. Notably, the GO/C-TMZ@PmAb + AMF group exhibited the greatest therapeutic effect, with controlled tumor growth and minimal systemic toxicity observed in healthy organs. These results underscore the efficacy of the GO/C-TMZ@PmAb MNP nanohybrid in enhancing glioblastoma treatment through targeted drug delivery and hyperthermia, providing a promising platform for further preclinical and clinical investigations.

Keywords: egfrviii expression; glioblastoma; magnetic hyperthermia; panitumumab conjugation; targeted drug delivery; temozolomide loading.