Large amino acid transporter 1 mediated glutamate modified docetaxel-loaded liposomes for glioma targeting

[Display omitted] Glutamate modified liposomes exhibit superior blood brain barrier transcytosis and glioma targeting dependent on large amino acid transporter 1. •Transporter-mediated nanoparticular drug delivery system.•Large amino acid transporter 1 mediated blood–brain barrier penetration and intracranial glioma targeting.•Docetaxel-loaded glutamate-TPGS functionalized liposomes enhanced the cell cytotoxicity.•Glutamate-TPGS functionalized liposomes improved BBB transcytosis ability and glioma cell uptake. 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.