Oncotarget

Research Papers:

Multifunctional targeting vinorelbine plus tetrandrine liposomes for treating brain glioma along with eliminating glioma stem cells

Xue‑tao Li, Wei Tang, Ying Jiang, Xiao‑min Wang, Yan‑hong Wang, Lan Cheng _ and Xian‑sheng Meng

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Oncotarget. 2016; 7:24604-24622. https://doi.org/10.18632/oncotarget.8360

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Abstract

Xue-tao Li1, Wei Tang2, Ying Jiang1, Xiao-min Wang1, Yan-hong Wang1, Lan Cheng1, Xian-sheng Meng1

1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China

2Linyi Food and Drug Testing Center, Linyi 276000, China

Correspondence to:

Lan Cheng, e-mail: chenglan1966@163.com

Keywords: multifunctional targeting liposomes, polyethylenimine, vapreotide, glioma stem cells, antitumor efficacy

Received: September 27, 2015     Accepted: March 04, 2016     Published: March 25, 2016

ABSTRACT

Malignant brain glioma is the most lethal and aggressive type of cancer. Surgery and radiotherapy cannot eliminate all glioma stem cells (GSCs) and blood–brain barrier (BBB) restricts the movement of antitumor drugs from blood to brain, thus leading to the poor prognosis with high recurrence rate. In the present study, the targeting conjugates of cholesterol polyethylene glycol polyethylenimine (CHOL-PEG2000-PEI) and D-a-tocopheryl polyethylene glycol 1000 succinate vapreotide (TPGS1000-VAP) were newly synthesized for transporting drugs across the BBB and targeting glioma cells and GSCs. The multifunctional targeting vinorelbine plus tetrandrine liposomes were constructed by modifying the targeting conjugates. The studies were undertaken on BBB model, glioma cells, GSCs, and glioma-bearing mice. In vitro results showed that multifunctional targeting drugs-loaded liposomes with suitable physicochemical property could enhance the transport drugs across the BBB, increase the intracellular uptake, inhibit glioma cells and GSCs, penetrate and destruct the GSCs spheroids, and induce apoptosis via activating related apoptotic proteins. In vivo results demonstrated that multifunctional targeting drugs-loaded liposomes could significantly accumulate into brain tumor location, show the specificity to tumor sites, and result in a robust overall antitumor efficacy in glioma-bearing mice. These data suggested that the multifunctional targeting vinorelbine plus tetrandrine liposomes could offer a promising strategy for treating brain glioma.


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