Borneol Enhances Angiopep-2 Modified Dendrimer Delivery of Doxorubicin Across the Blood-Brain Barrier for Improved Glioma Treatment

Borneol Enhances Angiopep-2 Modified Dendrimer Delivery of Doxorubicin Across the Blood-Brain Barrier for Improved Glioma Treatment

Glioma is the most common primary malignant brain tumor, posing significant challenges for effective treatment. Chemotherapy, a standard treatment approach, faces limitations due to the low permeability of drugs across the blood-brain barrier (BBB). This restricts the delivery of anti-tumor agents to the brain, hampering treatment efficacy.

Borneol, a time-honored 'Guide' drug in traditional Chinese medicine, has shown promise in promoting drug delivery to the brain. However, free drugs, particularly anti-glioma agents, risk being degraded and metabolized before reaching the tumor site, leading to potential side effects.

This study investigated whether borneol could enhance BBB penetration and improve glioma treatment in combination with a targeted drug delivery system (TDDS). The TDDS employed consisted of doxorubicin (DOX)-loaded PAMAM dendrimers modified with Angiopep-2, a ligand for the low-density lipoprotein receptor-related protein (LRP) that is overexpressed in both the BBB and gliomas.

The results demonstrated that:

• Angiopep-2 modification enhanced the affinity of the dendrimers to the target glioma cells, leading to increased cellular uptake and enhanced anti-tumor activity.* Borneol, when physically combined with the TDDS, further improved the anti-tumor efficacy of the system after crossing the BBB.* Compared to free DOX solution, the TDDS exhibited a sustained and pH-dependent drug release profile.

This innovative approach combining borneol with an Angiopep-2 modified dendrimer-based drug delivery system offers a promising strategy for enhancing the delivery of DOX across the BBB and improving the treatment of glioma. This synergistic approach warrants further investigation in clinical settings.