A novel synergetic targeting strategy for glioma therapy employing borneol combination with angiopep-2-modified, DOX-loaded PAMAM dendrimer

Abstract

Glioma is the most common primary malignant brain tumour and the effect of chemotherapy is hampered by low permeability across the blood–brain-barrier (BBB). Borneol is a time-honoured ‘Guide’ drug in traditional Chinese medicine and has been proved to be capable of promoting free drugs into the brain efficiently, but there are still risks that free drugs, especially anti-glioma drugs, may be disassembled and metabolised before penetrating the BBB and caused the whole brain distribution. The purpose of this paper was to investigate whether borneol intervention could facilitate the BBB penetration and assist glioma treatment by combining with doxorubicin (DOX) loaded PAMAM dendrimers drug delivery system modified with Angiopep-2 (a ligand of the low-density lipoprotein receptor-related protein, which overexpress both in the BBB and gliomas). The results demonstrated that Angiopep-2 modification could actually enhance the affinity between the dendrimers and the targeting cells and finally increase the cell uptake and boost the anti-tumour ability. Borneol physical combination could further enhance the anti-tumour efficiency of this targeting drug delivery system (TDDS) after penetrating BBB. Compared with free DOX solution, this TDDS illustrated obviously sustained and pH-dependent drug release. This suggested that this synergetic strategy provided a promising way for glioma therapy.

Keywords:

• Borneol
• Angiopep-2
• PAMAM dendrimer
• blood–brain barrier
• glioma

Acknowledgements

We thank Dr. Zhao Huajun (Department of Pharmacology, Zhejiang Chinese Medical University, China) for providing us with technical assistance. We thank Dr. Wang Meijiao and Zhu Feiye (Department of Analysis and Testing, Zhejiang Chinese Medical University, China) on the TEM and LSCM measurements.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was financially supported by National Natural Science Foundation of China (No. 81473361, 81673607 and 81603303) and New products of TCM Senile Diseases Co-Innovation Center of Hubei (No.15111903).