title: Multifunctional targeting vinorelbine plus tetrandrine liposomes for treating brain glioma along with eliminating glioma stem cells.
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.
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Xue-Tao
authors.initials: XT
authors.lastname: Li
authors.affiliation: Linyi Food and Drug Testing Center, Linyi 276000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Cheng
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Xian-Sheng
authors.initials: XS
authors.lastname: Meng
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000493:pharmacokinetics; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008081:Liposomes / Q000008:administration & dosage; D051379:Mice; D008813:Mice, Inbred ICR; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D011897:Random Allocation; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000077235:Vinorelbine
chemical_list: D044182:Benzylisoquinolines; D008081:Liposomes; C009438:tetrandrine; D014747:Vinblastine; D000077235:Vinorelbine
keywords: antitumor efficacy; glioma stem cells; multifunctional targeting liposomes; polyethylenimine; vapreotide