【摘 要】
：
LAT1 overexpressed on membrane of various tumor cells, are potential targets for tumor-targeting therapy.This study aimed to develop a LAT1-mediated drug de
【机 构】
：
State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmace
【出 处】
：
2015年第一届药代动力学朝阳论坛
论文部分内容阅读
LAT1 overexpressed on membrane of various tumor cells, are potential targets for tumor-targeting therapy.This study aimed to develop a LAT1-mediated drug delivery to target chemotherapeutic agents to LAT1-overexpressed tumor cells in vitro and in vivo.Here, different amino acids were attached to the N-terminal of DOX via the amido bond.After screening with S2-LAT1 model, the molecular Asp-DOX with a free carboxyl and a free amino group on the α-carbon atom of the Asp residue was an efficient compound.The product Asp-DOX was characterized by HPLC spectroscopy and mass spectrometry.In vitro, the Asp-DOX exerted stronger inhibition to the cancer cells (HepG2, HCT116 and MCF7) overexpressing LAT1 and the uptake of Asp-DOX was about 3.5-fold higher than that of DOX in HepG2 cells.Data of pharmacokinetics showed that Asp-DOX expressed a longer circulation time (t1/2 =49.14 min) in the blood compared to DOX (t1/2=19.12 min).
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