A Brain-Targeting NIR-II Ferroptosis System: Effective Visualization and Oncotherapy for Orthotopic Glioblastoma

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Near-infrared-II (NIR-II) ferroptosis activators show promise for deep tumor theranostics, but nonvisual iron-based systems limit in vivo study and can cause off-target effects.
• Gold (Au) nanoparticles can target tumor cells, offering potential for improved specificity in cancer theranostics.

Purpose of the Study:

• To develop novel Au(I)-based NIR-II ferroptosis nanoparticles (TBTP-Au NPs) for brain-targeted orthotopic glioblastoma theranostics.
• To enable real-time visual monitoring of blood-brain barrier (BBB) penetration and glioblastoma targeting.
• To investigate a new Au(I)-mediated ferroptosis mechanism for glioma treatment.

Main Methods:

• Construction of Au(I)-based NIR-II ferroptosis nanoparticles (TBTP-Au NPs).
• In vivo theranostic studies in orthotopic glioblastoma mouse models.
• Real-time visual monitoring of BBB penetration and tumor targeting using NIR-II imaging.
• Validation of heme oxygenase-1-regulated ferroptosis activation by released TBTP-Au.

Main Results:

• TBTP-Au NPs achieved real-time visual monitoring of BBB penetration and glioblastoma targeting.
• The released TBTP-Au specifically activated heme oxygenase-1-regulated ferroptosis in glioma cells.
• Significant extension of survival time in glioma-bearing mice was observed.

Conclusions:

• Au(I)-based TBTP-Au NPs offer a novel, visual theranostic platform for glioblastoma.
• This study validates a new Au(I)-mediated ferroptosis mechanism for targeted cancer therapy.
• The findings suggest a potential new strategy for developing advanced, high-specificity visual anticancer drugs for clinical trials.