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      Smart Human-Serum-Albumin-As2 O3 Nanodrug with Self-Amplified Folate Receptor-Targeting Ability for Chronic Myeloid Leukemia Treatment.

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          Abstract

          Arsenic trioxide (ATO, As2 O3 ) 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.

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          Author and article information

          Journal
          Angew. Chem. Int. Ed. Engl.
          Angewandte Chemie (International ed. in English)
          Wiley
          1521-3773
          1433-7851
          Aug 28 2017
          : 56
          : 36
          Affiliations
          [1 ] Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Life Sciences, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China.
          [2 ] Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, China.
          [3 ] 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.
          [4 ] Department of Chemistry, Department of Physiology and Functional Genomics, Center for Research at Bio/Nano Interface, UF Health Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, FL, 32611-7200, USA.
          Article
          NIHMS905352
          10.1002/anie.201701366
          5912668
          28686804
          1c91e652-2d46-4a46-9e1e-b01d6c242869
          History

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

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