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Smart Human‐Serum‐Albumin–As 2 O 3 Nanodrug with Self‐Amplified Folate Receptor‐Targeting Ability for Chronic Myeloid Leukemia Treatment
Author(s) -
Peng Yongbo,
Zhao Zilong,
Liu Teng,
Li Xiong,
Hu Xiaoxiao,
Wei Xiaoping,
Zhang Xiaobing,
Tan Weihong
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201701366
Subject(s) - arsenic trioxide , myeloid leukemia , acute promyelocytic leukemia , downregulation and upregulation , glutathione , in vivo , cancer research , human serum albumin , leukemia , chemistry , folate receptor , pharmacology , in vitro , cancer , medicine , cancer cell , immunology , apoptosis , biochemistry , biology , gene , retinoic acid , microbiology and biotechnology , enzyme
Arsenic trioxide (ATO, As 2 O 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.