title: Multifunctional targeting daunorubicin plus quinacrine liposomes, modified by wheat germ agglutinin and tamoxifen, for treating brain glioma and glioma stem cells.
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.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China; School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China.
authors.forename: Xue-Tao
authors.initials: XT
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Rui-Jun
authors.initials: RJ
authors.lastname: Ju
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Cheng-Xiang
authors.initials: CX
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Meng-Ge
authors.initials: MG
authors.lastname: Sun
authors.affiliation: Institute of Clinical Medical Sciences, Chia-Japan Friendship Hospital, The Ministry of Health, Beijing, China.
authors.forename: Jin-Ning
authors.initials: JN
authors.lastname: Lou
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Wan-Liang
authors.initials: WL
authors.lastname: Lu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D011796:Quinacrine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013629:Tamoxifen / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D014909:Wheat Germ Agglutinins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D008081:Liposomes; D014909:Wheat Germ Agglutinins; D013629:Tamoxifen; D011796:Quinacrine; D003630:Daunorubicin