Specific anti-glioma targeted-delivery strategy of engineered small extracellular vesicles dual-functionalised by...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Neuro-oncology

Background:

• Glioma is a deadly brain tumor with limited treatment options due to the blood-brain barrier (BBB).
• Developing effective drug delivery systems that can cross the BBB and target brain tumors is crucial for improving patient outcomes.

Purpose of the Study:

• To engineer small extracellular vesicles (sEVs) with dual-targeting capabilities for enhanced glioma chemotherapy.
• To evaluate the efficiency of these modified sEVs in crossing the BBB and targeting brain tumors in vitro and in vivo.

Main Methods:

• Small extracellular vesicles (sEVs) were modified with Angiopep-2 and trans-activator of transcription peptides for dual targeting.
• The targeting efficiency of engineered sEVs across the BBB and to glioma cells was assessed in vitro using cell cultures and a BBB model.
• The efficacy of doxorubicin-loaded, dual-modified sEVs was evaluated in subcutaneous and orthotopic glioma mouse models.

Main Results:

• Engineered sEVs demonstrated high efficiency in targeting the BBB and glioma cells in vitro.
• In vivo studies confirmed the BBB penetration and glioma targeting capabilities of the dual-modified sEVs.
• Dual-modified sEVs loaded with doxorubicin significantly improved the survival time of glioma-bearing mice by over 2-fold with minimal side effects.

Conclusions:

• Dual-modified sEVs represent a promising drug delivery platform for overcoming the BBB and treating brain tumors like glioma.
• This strategy offers an efficient and specific approach for chemotherapy delivery, holding potential for treating central nervous system diseases.