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

被引:27
|
作者
Liu, Shuang [1 ]
Zhang, Shi-meng [2 ]
Ju, Rui-jun [3 ]
Xiao, Yao [1 ]
Wang, Xin [1 ]
Song, Xiao-li [1 ]
Gu, Li-yan [1 ]
Cheng, Lan [1 ]
Li, Xue-tao [1 ]
Chen, Gui-rong [1 ]
机构
[1] Liaoning Univ Tradit Chinese Med, Sch Pharm, Shengming 1 Rd 77, Dalian 116600, Peoples R China
[2] Linyi Peoples Hosp, Dept Neurol, Linyi 276003, Peoples R China
[3] Beijing Inst Petrochem Technol, Dept Pharmaceut Engn, Beijing 102617, Peoples R China
基金
中国国家自然科学基金;
关键词
Daunorubicin; Honokiol; Lactoferrin; Vasculogenic mimicry; Tumor cell invasion; Blood-brain barrier; VASCULOGENIC MIMICRY CHANNELS; INVASIVE BREAST-CANCER; IN-VITRO; PROCATIONIC LIPOSOMES; STEM-CELLS; DELIVERY; THERAPY; VIVO; EPIRUBICIN; PACLITAXEL;
D O I
10.1016/j.ejps.2017.06.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:185 / 197
页数:13
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