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      Smart human serum albumin-As 2O 3 nanodrug with self-amplified folate receptor-targeting ability for chronic myeloid leukemia treatment

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          Abstract

          Arsenic trioxide (ATO, As 2O 3) is currently used to treat acute promyelocytic leukemia. However, expanding its use to include high-dose treatment of other cancers is severely hampered by serious side effects on healthy organs. To address these limitations, we loaded ATO onto folate (FA)-labeled human serum albumin (HSA) pretreated with glutathione (GSH) based on the low pH- and GSH-sensitive arsenic-sulfur bond, and we termed the resulting smart nanodrug as FA-HSA-ATO. FA-HSA-ATO could specifically recognize folate receptor-β-positive (FRβ+) chronic myeloid leukemia (CML) cells, resulting in more intracellular accumulation of ATO. Furthermore, the nanodrug could upregulate FRβ expression in CML cancer cells and xenograft tumor model, facilitating even more recruitment and uptake of FRβ-targeting drugs. In vitro and in vivo experiments indicate that the nanodrug significantly alleviates side effects and improves therapeutic efficacy of ATO on CML and xenograft tumor model.

          COMMUNICATION

          As 2O 3 (ATO) was loaded onto folate (FA)-labeled human serum albumin (HSA) pretreated with glutathione based on low pH- and GSH-sensitive arsenic-sulfur bond formation to produce smart nanodrug FA-HSA-ATO. The nanodrug could upregulate FRβ expression in CML, facilitating even more recruitment and uptake of FRβ-targeting drugs. In vitro and in vivo experiments indicate the nanodrug significantly improves therapeutic efficacy of ATO in CML treatment.

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          Author and article information

          Contributors
          Journal
          0370543
          537
          Angew Chem Int Ed Engl
          Angew. Chem. Int. Ed. Engl.
          Angewandte Chemie (International ed. in English)
          1433-7851
          1521-3773
          3 April 2018
          04 August 2017
          28 August 2017
          28 August 2018
          : 56
          : 36
          : 10845-10849
          Affiliations
          Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082 (China)
          Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082 (China)
          Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082 (China)
          Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008 (China)
          Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008 (China)
          Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082 (China)
          Center for Clinical Molecular Medicine, Ministry of Education Key Laboratory of Child Development and Dis-orders, Children's Hospital of Chongqing Medical University, Chongqing 400014 (China)
          Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082 (China)
          Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082 (China)
          Department of Chemistry, Department of Physiology and Functional Genomics, Center for Research at Bio/Nano Interface, Shands Cancer Center, University of Florida Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, FL 32611-7200 (USA)
          Author notes
          [†]

          These authors contributed equally to this work.

          Article
          PMC5912668 PMC5912668 5912668 nihpa905352
          10.1002/anie.201701366
          5912668
          28686804
          1c91e652-2d46-4a46-9e1e-b01d6c242869
          History
          Categories
          Article

          arsenic trioxide,human serum albumin,smart nanodrug,chronic myeloid leukemia,folate receptor-β

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