Vinorelbine cationic liposomes modified with wheat germ agglutinin for inhibiting tumor metastasis in treatment of brain glioma.

Abstract

Glioma is the most common primary malignant brain tumor with a poor prognosis. The application of chemotherapeutic drugs is limited due to the existence of blood-brain barrier and serious side effects. Liposomes have been proven to be a stable and useful drug delivery system for tumors. In this paper, WGA (wheat germ agglutinin) modified vinorelbine cationic liposomes had been successfully constructed for treating glioma. In the liposomes, WGA was modified on the liposomal surface for crossing the blood-brain barrier and increasing the targeting effects, 3-(N-(N', N'-dimethylaminoethane) carbamoyl) cholesterol (DC-Chol) was used as cationic material and vinorelbine was encapsulated in the aqueous core of liposomes to inhibit tumor metastasis and kill tumor cells. Studies were performed on C6 cells in vitro and were verified in brain glioma-bearing mice in vivo. Results in vitro demonstrated that the targeting liposomes could induce C6 cells apoptosis, promote drugs across the blood-brain barrier, inhibit the metastasis of tumor cells and increase targeting effects to tumor cells. Meanwhile, action mechanism studies showed that the targeting liposomes could down-regulate PI3K, MMP-2, MMP-9 and FAK to inhibit tumor metastasis. Results in vivo exhibited that the targeting liposomes displayed an obvious antitumor efficacy by accumulating selectively in tumor site and exhibited low toxicity to blood system and major organs. Hence, WGA modified vinorelbine cationic liposomes might provide a safe and efficient therapy strategy for glioma.

• Authors: Yao Xiao, Lan Cheng, Hong-Jun Xie, Rui-Jun Ju, Xin Wang, Min Fu, Jing-Jing Liu, Xue-Tao Li
• Journal: Artificial cells, nanomedicine, and biotechnology (Artif Cells Nanomed Biotechnol) Vol. 46 Issue sup3 Pg. S524-S537 ( 2018) ISSN: 2169-141X [Electronic] England
• PMID: 30299160 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Liposomes
• Neoplasm Proteins
• Wheat Germ Agglutinins
• Vinorelbine

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, pharmacokinetics, pharmacology)
• Brain Neoplasms (drug therapy, metabolism, pathology)
• Down-Regulation (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Glioma (drug therapy, metabolism, pathology)
• Liposomes
• Mice
• Neoplasm Metastasis
• Neoplasm Proteins (biosynthesis)
• Vinorelbine (chemistry, pharmacokinetics, pharmacology)
• Wheat Germ Agglutinins (chemistry, pharmacokinetics, pharmacology)