Antitumor efficacy of Lf modified daunorubicin plus honokiol liposomes in treatment of brain glioma.

Abstract

Malignant brain glioma is the most common and aggressive type of primary intracranial neoplasm. Regular chemotherapy cannot eradicate brain glioma cells and the residual glioma cells could form vasculogenic mimicry (VM) channels under hypoxic conditions to provide nutrients for tumor cell invasion. In addition, the existence of the blood-brain barrier (BBB) restricts most antitumor drugs into brain glioma. In this study, we developed a kind of lactoferrin (Lf) modified daunorubicin plus honokiol liposomes to transport antitumor drugs across BBB, eliminate the VM channels and block tumor cell invasion. The evaluations were performed on BBB model, brain glioma cells and glioma-bearing mice. In vitro results showed that the targeting liposomes with suitable physicochemical property could enhance the drug transportation acrossing the BBB, inhibit C6 cells invasion and destroy VM channels. Action mechanism studies indicated that Lf modified daunorubicin plus honokiol liposomes could activate apoptotic enzymes caspase 3 as well as down-regulate VM protein indicators (PI3K, MMP-2, MMP-9, VE-Cadherin and FAK). In vivo results displayed the targeting liposomes improved accumulation in brain tumor tissue and exhibited obvious antitumor efficacy. Therefore, Lf modified daunorubicin plus honokiol liposomes could be used as a potential therapy for treatment of brain glioma.

• Authors: Shuang Liu, Shi-Meng Zhang, Rui-Jun Ju, Yao Xiao, Xin Wang, Xiao-Li Song, Li-Yan Gu, Lan Cheng, Xue-Tao Li, Gui-Rong Chen
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 106 Pg. 185-197 (Aug 30 2017) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 28583810 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier B.V.

Chemical References

• Antibiotics, Antineoplastic
• Biphenyl Compounds
• Lignans
• Liposomes
• honokiol
• Lactoferrin
• Daunorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, chemistry, therapeutic use)
• Apoptosis (drug effects)
• Biphenyl Compounds (administration & dosage, chemistry, therapeutic use)
• Blood-Brain Barrier (metabolism)
• Brain Neoplasms (drug therapy)
• Cell Line, Tumor
• Daunorubicin (administration & dosage, chemistry, therapeutic use)
• Drug Liberation
• Glioma (drug therapy)
• Lactoferrin (administration & dosage, chemistry, therapeutic use)
• Lignans (administration & dosage, chemistry, therapeutic use)
• Liposomes
• Mice, Inbred ICR
• Rats