Oncotarget

Research Papers:

Multifunctional targeting daunorubicin plus quinacrine liposomes, modified by wheat germ agglutinin and tamoxifen, for treating brain glioma and glioma stem cells

Xue-Tao Li, Rui-Jun Ju, Xiu-Ying Li, Fan Zeng, Ji-Feng Shi, Lei Liu, Cheng-Xiang Zhang, Meng-Ge Sun, Jin-Ning Lou and Wan-Liang Lu _

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Oncotarget. 2014; 5:6497-6511. https://doi.org/10.18632/oncotarget.2267

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Abstract

Xue-Tao Li1,2, Rui-Jun Ju1, Xiu-Ying Li1, Fan Zeng1, Ji-Feng Shi1, Lei Liu1, Cheng-Xiang Zhang1, Meng-Ge Sun1, Jin-Ning Lou3 and Wan-Liang Lu1

1 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China

2 School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China

3 Institute of Clinical Medical Sciences, Chia-Japan Friendship Hospital, The Ministry of Health, Beijing, China

Correspondence:

Wan-Liang Lu, email:

Keywords: multifunctional targeting liposomes, wheat germ agglutinin, daunorubicin, tamoxifen, brain glioma stem cells

Received: May 08, 2014 Accepted: July 26, 2014 Published: July 26, 2014

Abstract

Most anticancer drugs are not able to cross the blood-brain barrier (BBB) effectively while surgery and radiation therapy cannot eradicate brain glioma cells and glioma stem cells (GSCs), hence resulting in poor prognosis with high recurrence rates. In the present study, a kind of multifunctional targeting daunorubicin plus quinacrine liposomes was developed for treating brain glioma and GSCs. Evaluations were performed on in-vitro BBB model, murine glioma cells, GSCs, and GSCs bearing mice. Results showed that the multifunctional targeting daunorubicin plus quinacrine liposomes exhibited evident capabilities in crossing the BBB, in killing glioma cells and GSCs and in diminishing brain glioma in mice. Action mechanism studies indicated that the enhanced efficacy of the multifunctional targeting drugs-loaded liposomes could be due to the following aspects: evading the rapid elimination from blood circulation; crossing the BBB effectively; improving drug uptake by glioma cells and GSCs; down-regulating the overexpressed ABC transporters; inducing apoptosis of GSCs via up-regulating apoptotic receptor/ligand (Fas/Fasl), activating apoptotic enzymes (caspases 8, 9 and 3), activating pro-apoptotic proteins (Bax and Bok), activating tumor suppressor protein (P53) and suppressing anti-apoptotic proteins (Bcl-2 and Mcl-1). In conclusion, the multifunctional targeting daunorubicin plus quinacrine liposomes could be used as a potential therapy for treating brain glioma and GSCs.


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