LAT1 targeted brain delivery of temozolomide and sorafenib for effective glioma therapy  

作　　者：Yufei Zhang Qian Cheng Yuhao Xue Kai Yao Madiha Zahra Syeda Jian Xu Jianheng Wu Zhenjie Wang Longguang Tang Qingchun Mu 

机构地区：[1]Department of Physiology,Basic Medical College,Guilin Medical University,Guilin 541199,China [2]College of Pharmacy,Guilin Medical University,Guilin 541199,China [3]College of Life Science,Mudanjiang Medical University,Mudanjiang 157011,China [4]Department of Neurosurgery,First Affiliated Hospital of Harbin Medical University,Harbin 150001,China [5]Affiliated Gaozhou People’s Hospital,Guangdong Medical University,Maoming 525200,China [6]International Institutes of Medicine,The Fourth Affiliated Hospital,Zhejiang University School of Medicine,Yiwu 322000,China

出　　处：《Nano Research》2023年第7期9743-9751,共9页纳米研究（英文版）

基　　金：This work was supported by the National High Technology Research and Development Program of China(No.2019YFC0121000);the National Natural Science Foundation of China(Nos.32201127 and 82270113);Medical Scientific Research Foundation of Guangdong Province,China(No.A2021298).

摘　　要：Glioma is the most common primary craniocerebral tumor caused by the cancerous growth of glial cells in the brain and spinal cord.Currently,standard treatment is the surgical resection followed by concurrent radiation and chemotherapy.However,the blood-brain barrier(BBB)prevents most antitumor drugs from entering the brain and reduces their efficacy,especially in lowgrade glioma.Since L-type amino acid transporter 1(LAT1)is highly expressed in glioma cells and mediates drug transport across the BBB,it is a promising target for drug delivery and treatment of glioma.Temozolomide(TMZ)is the first-line treatment for glioma,however,patients often exhibit drug resistance at advanced stage.A multikinase inhibitor and inducer of ferroptosis,sorafenib can improve the therapeutic effects of TMZ.Therefore,to optimize the glioma treatment and cross the BBB,we designed LAT1-targeting nanoparticles co-loaded with TMZ and sorafenib.Our results from both in vitro and in vivo studies confirmed that LAT1-targeting nanoparticles significantly increased the cellular uptake,cytotoxicity,accumulation at tumor site,and the anti-tumor efficacy compared to the non-target nanoparticles.Therefore,LAT1 can be used as a potential target for braintargeted drug delivery,and sorafenib-induced ferroptosis can aid the anti-glioma efficacy of TMZ.

关 键 词：L-type amino acid transporter 1(LAT1) GLIOMA blood-brain barrier(BBB) ferroptosis drug delivery 

分 类 号：R730.5[医药卫生—肿瘤]