Development of Angiopep-2 targeted dendrimer-based nanotheranostic system for enhanced temozolomide delivery to glioblastoma multiforme

Abstract

Abstract Background Glioblastoma multiforme remains a challenging cancer to treat effectively. This study focuses on developing a novel nanotheranostic platform to improve targeted temozolomide delivery and enhance glioblastoma multiforme treatment. Results This study successfully developed a multifunctional nanocarrier system utilizing fourth-generation polypropylene imine (PPI) dendrimers, functionalized with polyethylene glycol (PEG) for enhanced biocompatibility and conjugated with Angiopep-2 (ANG-2) for targeted delivery to glioblastoma multiforme cells. Incorporating silver sulfide (Ag2S) quantum dots conferred near-infrared (NIR) imaging capabilities, enabling noninvasive real-time monitoring. Comprehensive characterization using FTIR, NMR, and mass spectrometry validated the successful synthesis, functionalization, and encapsulation of the nanocarrier, with evidence of efficient loading of temozolomide (TMZ) at 56.32 ± 2.8%. In vitro drug release studies demonstrated a sustained release profile, achieving 52.86 ± 2.09% release within 24 h. Ex vivo studies revealed significantly enhanced cellular uptake and cytotoxicity against BCECs and C6 glioma cells compared to free TMZ, while in vivo biodistribution studies confirmed targeted accumulation of the nanocarrier in tumor tissues, as visualized through NIR imaging. Conclusions This study highlights the significant potential of the developed dendrimer-based nanotheranostic system as an innovative platform for glioblastoma multiforme treatment. The successful integration of fourth-generation PPI dendrimers, PEG functionalization, ANG-2 targeting ligands, and Ag2S quantum dots enabled precise imaging-guided delivery and targeted temozolomide therapy. The system demonstrated excellent biocompatibility, high drug-loading capacity, sustained drug release, enhanced cellular uptake, and tumor-specific accumulation, translating into superior therapeutic efficacy and real-time imaging capabilities. These findings highlight the promise of this multifunctional nanoplatform in addressing the challenges of glioblastoma therapy and pave the way for future clinical translation in personalized cancer treatment.

Keywords

• Nanotheranostics
• Glioblastoma multiforme
• Temozolomide
• Polyethylene glycol
• Angiopep-2
• Drug targeting