SChitosan-capped gold nanoparticles impair radioresistant glioblastoma stem-like cells

Area of Science:

• Nanomedicine
• Biomaterials Science
• Oncology

Background:

• Glioblastoma (GBM) is a lethal brain tumor characterized by chemo- and radioresistant glioblastoma stem cells (GSCs).
• Overcoming drug resistance in GSCs is crucial for effective GBM treatment.
• Current therapeutic strategies face limitations due to poor drug penetration and GSC resistance.

Purpose of the Study:

• To investigate the potential of chitosan-capped gold nanoparticles (Chit-GNPs) to enhance drug delivery and therapeutic efficacy in glioblastoma.
• To evaluate the cellular uptake and cytotoxicity of Chit-GNPs in GSCs.
• To determine if Chit-GNPs can improve the response of GSCs to irradiation.

Main Methods:

• Chit-GNPs were synthesized using chitosan as a reducing and stabilizing agent.
• Characterization of Chit-GNPs included spectroscopy, electron microscopy, and zeta potential measurements.
• Patient-derived GSCs and human osteoblasts were treated with Chit-GNPs and/or irradiation, followed by assessment of nanoparticle uptake and cytotoxicity.

Main Results:

• Positively-charged, 26 nm spherical Chit-GNPs demonstrated significant intracellular accumulation in GSCs, unlike uncoated gold nanoparticles (GNPs).
• Chit-GNPs exhibited high cytotoxicity against GSCs, independent of irradiation, and showed selective toxicity towards GSCs without affecting normal osteoblasts.
• Irradiation did not enhance the therapeutic benefit when combined with Chit-GNPs or uncoated GNPs.

Conclusions:

• Chit-GNPs exhibit substantial internalization and selective cytotoxicity in GSCs, highlighting their potential as an anticancer agent.
• Chit-GNPs represent a promising platform for drug delivery in glioblastoma treatment.
• The findings suggest Chit-GNPs could overcome GSC resistance mechanisms in glioblastoma therapy.