title: Multifunctional Tandem Peptide Modified Paclitaxel-Loaded Liposomes for the Treatment of Vasculogenic Mimicry and Cancer Stem Cells in Malignant Glioma.
abstract: The chemotherapy of aggressive glioma is usually accompanied by a poor prognosis because of the formation of vasculogenic mimicry (VM) and brain cancer stem cells (BCSCs). VM provided a transporting pathway for nutrients and blood to the extravascular regions of the tumor, and BCSCs were always related to drug resistance and the relapse of glioma. Thus, it is important to evaluate the inhibition effect of antiglioma drug delivery systems on both VM and BCSCs. In this study, paclitaxel-loaded liposomes modified with a multifunctional tandem peptide R8-c(RGD) (R8-c(RGD)-Lip) were used for the treatment of glioma. An in vitro cellular uptake study proved the strongest targeting ability to be that of R8-c(RGD)-Lip to glioma stem cells. Drug loaded R8-c(RGD)-Lip exhibited an efficient antiproliferation effect on BCSCs and could induce the destruction of VM channels in vitro. The following pharmacodynamics study demonstrated that R8-c(RGD)-modified drug-loaded liposomes achieved both anti-VM and anti-BCSC effects in vivo. Finally, no significant cytotoxicity of the blood system or major organs of the drug-loaded liposomes was observed under treatment dosage in the safety evaluation. In conclusion, all of the results proved that R8-c(RGD)-Lip was a safe and efficient antiglioma drug delivery system.
authors.affiliation: †Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Yayuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: †Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Mei
authors.affiliation: †Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Qianwen
authors.initials: Q
authors.lastname: Yu
authors.affiliation: ‡Sichuan Academy of Chinese Medicine Sciences, No. 51, Block 4, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Xu
authors.affiliation: †Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: †Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Yang
authors.affiliation: †Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Kairong
authors.initials: K
authors.lastname: Shi
authors.affiliation: †Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Qianyu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: †Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.affiliation: †Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: †Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: He
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma; D008081:Liposomes / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D017239:Paclitaxel
keywords: antiglioma; brain cancer stem cells; cell penetrating peptide; tandem peptide; vasculogenic mimicry