title: Large amino acid transporter 1 mediated glutamate modified docetaxel-loaded liposomes for glioma targeting.
abstract: The therapeutic outcome of glioma treatment is rigorously limited by blood-brain barrier (BBB) and infiltrating growth of glioma. To tackle the dilemma, more and more attentions were focused on developing nutrient transporters-mediated dual-targeted drug delivery system, in one side for BBB penetration, another for intracranial glioma targeting. Herein, Large amino acid transporter 1 (LAT1), overexpressed both on BBB and glioma cells, was selected as a target. Docetaxel-loaded glutamate-d-α-tocopherol polyethylene glycol 1000 succinate copolymer (Glu-TPGS) functionalized LAT1-targeting liposomes (DTX-TGL) were applied to enhance the BBB penetration and glioma therapy. The in vivo results of the fluorescent image indicated that TGL possessed an effective BBB penetration than that of unmodified ones in mice. The LAT1 targeting effcicacy and cell cytotoxicity of TGL were investigated in C6 glioma cells. Compared with unmodified liposomes, a significant higher cellular uptake and cell cytotoxicity was found in TGL treated group. Our results indicated that LAT1-targeting docetaxel-loaded liposome paves up a new direction using LAT1 transporter as a good target in designing brain glioma-targeting nanosystems.
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
authors: Lin
authors: L
authors: Li
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
authors: Xingsheng
authors: X
authors: Di
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
authors: Shenwu
authors: S
authors: Zhang
authors: Department of Pharmacology, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
authors: Qiming
authors: Q
authors: Kan
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
authors: Hao
authors: H
authors: Liu
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
authors: Tianshu
authors: T
authors: Lu
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
authors: Yongjun
authors: Y
authors: Wang
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
authors: Qiang
authors: Q
authors: Fu
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China; Municipal Key Laboratory of Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China. Electronic address: sunjin66@21cn.com.
authors: Jin
authors: J
authors: Sun
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China. Electronic address: hezhonggui@vip.163.com.
authors: Zhonggui
authors: Z
authors: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D018698:Glutamic Acid / Q000737:chemistry* / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000737:chemistry* / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D014810:Vitamin E / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D027283:Large Neutral Amino Acid-Transporter 1; D008081:Liposomes; D043823:Taxoids; D014810:Vitamin E; D000077143:Docetaxel; D018698:Glutamic Acid; C014225:tocophersolan
keywords: Blood–brain-barrier; Docetaxel; Glioma; LAT1; Liposomes