title: Chloride channel-mediated brain glioma targeting of chlorotoxin-modified doxorubicine-loaded liposomes.
abstract: The chlorotoxin (ClTx), a scorpion-derived peptide, binding to gliomas with high specificity, was firstly applied to establish the ClTx-modified doxorubicin (DOX)-loaded liposome delivery system for targeting the brain glioma and improving the anticancer efficacy. In vitro physicochemical characterization of the novel liposome system presented satisfactory size of 100 nm with uniform distribution, high encapsulation efficiency and adequate loading capacity of both fluorescent probe and anticancer drug. It was demonstrated quantitatively by the spectrophotofluorometry and flow cytometry and qualitatively by the confocal microscopy that ClTx highly facilitated the uptake of liposomes by three glioma cell lines and one endothelial cell line. In vitro cytotoxicity studies proved that the presence of ClTx increased the cytotoxicity against glioma cells and endothelial cells with various levels for different cell lines. In BALB/c mice bearing U87 tumor xenografts, biodistribution of DiR-loaded liposomes by body imaging and anti-glioma pharmacodynamics of DOX-loaded liposomes were investigated. The ClTx-modified liposomes showed more accumulation in the subcutaneous and intracranial tumors, higher tumor growth inhibition and lower blood toxicity in the armpit tumor model. The in vitro and in vivo results exhibited good correlation of glioma targeting of the ClTx-modified liposomes. Significantly, with the ClTx as the targeting ligand, the liposomes might serve as an applicable delivery system for brain glioma therapy or imaging.
authors: Yu
authors: Y
authors: Xiang
authors: Liang
authors: L
authors: Liang
authors: Xueqing
authors: X
authors: Wang
authors: Jiancheng
authors: J
authors: Wang
authors: Xuan
authors: X
authors: Zhang
authors: Qiang
authors: Q
authors: Zhang
mesh_terms: D000818:Animals; D001682:Biological Availability; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D007958:Leukocyte Count; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D055672:Static Electricity; D051598:Whole Body Imaging; D023041:Xenograft Model Antitumor Assays
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D018118:Chloride Channels; D005456:Fluorescent Dyes; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D012604:Scorpion Venoms; C091539:Chlorotoxin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol