title: Amino Acid Metabolism Abnormity and Microenvironment Variation Mediated Targeting and Controlled Glioma Chemotherapy.
abstract: Energy metabolism abnormity is one of the most significant hallmarks of cancer. As a result, large amino acid transporter 1 (LAT1) is remarkably overexpressed in both blood-brain-barrier and glioma tumor cells, leading a rapid and sufficient substrate transportation. 3CDIT and 4CDIT are originally synthesized by modifying the existing most potent LAT1 substrate. 3CDIT is selected as its higher glioma-targeting ability. Since the microenvironment variation in tumor cells is another important feature of cancer, a great disparity in adenosine-5'-triphosphate (ATP) and glutathione (GSH) levels between extracellular and intracellular milieu can provide good possibilities for dual-responsive drug release in tumor cells. Doxorubicin (DOX) is successfully intercalated into the ATP aptamer DNA scaffolds, compressed by GSH-responsive polymer pOEI, and modified with 3CDIT to obtain 3CDIT-targeting pOEI/DOX/ATP aptamer nanoparticles (NPs). Enhanced NP accumulation and rapid GSH & ATP dual-responsive DOX release in glioma are demonstrated both in vitro and in vivo. More efficient therapeutic effects are shown with 3CDIT-targeting pOEI/DOX/ATP aptamer NPs than free DOX and no systemic toxicity is observed. Therefore, glioma-targeting delivery and GSH & ATP dual-responsive release guarantee an adequate DOX accumulation within tumor cells and ensure a safe and efficient chemotherapy for glioma.
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, P. R. China.
authors: Sai
authors: S
authors: An
authors: Department of Medical Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, P. R. China.
authors: Xiuhong
authors: X
authors: Lu
authors: Department of Medical Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, P. R. China.
authors: Weili
authors: W
authors: Zhao
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, P. R. China.
authors: Tao
authors: T
authors: Sun
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, P. R. China.
authors: Yu
authors: Y
authors: Zhang
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, P. R. China.
authors: Yifei
authors: Y
authors: Lu
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, P. R. China. jiangchen@shmu.edu.cn.|State Key Laboratory of Medical Neurobiology, Fudan University, 826 Zhangheng Road, Shanghai, 201203, P. R. China. jiangchen@shmu.edu.cn.
authors: Chen
authors: C
authors: Jiang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D027283:Large Neutral Amino Acid-Transporter 1; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D005978:Glutathione
keywords: amino acids; cancer treatment; chemotherapy; drug delivery; glioma