All-stage targeted therapy for glioblastoma based on lipid membrane coated cabazitaxel nanocrystals.

Abstract

Glioblastoma (GBM) is the most aggressive brain tumor with poor prognosis and frequent recurrence. The blood-brain barrier (BBB), blood-brain tumor barrier (BBTB) hinder the entry of therapeutics into the glioma region. Vasculogenic mimicry (VM) formed by invasive glioma cells is also related to recurrence of GBM. VAP is a D-peptide ligand of GRP78 protein overexpressed on BBTB, VM, and glioma cells but not on normal tissues. Besides, p-hydroxybenzoic acid (pHA) can effectively traverse the BBB. Herein we developed an all-stage glioma-targeted cabazitaxel (CBZ) nanocrystal loaded liposome modified with a "Y" shaped targeting ligand composed of pHA and VAP (pV-Lip/cNC). The pure drug nanocrystal core provided high drug loading, while lipid membrane promoted the stability and circulation time. pV-Lip/cNC exhibited excellent glioma homing, barriers crossing, and tumor spheroid penetrating capability in vitro. Treatment of pV-Lip/cNC displayed enhanced CBZ accumulation in glioma and anti-glioma effect with a median survival time (53 days) significantly longer than that of cNC loaded liposomes modified with either single ligand (42 days for VAP and 45 days for pHA) in the murine orthotopic GBM model. These results indicated pV-Lip/cNC could traverse the BBB and BBTB, destruct VM, and finally kill glioma cells to realize all-stage glioma therapy.

• Authors: Sunyi Wu, Linwei Lu, Jianfen Zhou, Danni Ran, Songli Wang, Qianzhu Xu, Weixia Xu, Jun Wang, Yu Liu, Cao Xie, Zimiao Luo, Weiyue Lu
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 345 Pg. 685-695 (05 2022) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 35346767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022. Published by Elsevier B.V.

Chemical References

• Ligands
• Lipids
• Liposomes
• Taxoids
• cabazitaxel

Topics

• Animals
• Blood-Brain Barrier (metabolism)
• Brain Neoplasms (metabolism)
• Cell Line, Tumor
• Drug Delivery Systems
• Glioblastoma (drug therapy, metabolism)
• Glioma (drug therapy, metabolism)
• Ligands
• Lipids (therapeutic use)
• Liposomes (metabolism)
• Mice
• Nanoparticles
• Taxoids