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Issue 47, 2019
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Sgc8 aptamer targeted glutathione-responsive nanoassemblies containing Ara-C prodrug for the treatment of acute lymphoblastic leukemia

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Abstract

Cytarabine (Ara-C) is an essential medicine used in the clinical treatment of acute lymphoblastic leukemia. However, Ara-C suffers from high hydrophilicity, rapid plasma degradation and significant side effects. Thus, herein, to eliminate the limitations of Ara-C in the treatment of leukemia, Sgc8 aptamer targeting and glutathione (GSH)-responsive polymeric micelles (PCL-ss-Ara@Sgc8-BSA) were prepared. The prodrug was synthesized via covalent bond formation between acryloyl chloride-terminal PCL-ss-PCL and Ara-C, and surface decoration with Sgc8-bovine serum albumin (Sgc8-BSA). The obtained PCL-ss-Ara@Sgc8-BSA exhibited good GSH-responsive drug release behavior, obvious targetability and sufficient antitumor effect to acute lymphoblastic leukemia (ALL) cells (CCRF-CEM). A hemolysis test was further carried out to demonstrate that these polymeric micelles are safe to be administrated intravenously. Compared with free Ara-C, PCL-ss-Ara@Sgc8-BSA significantly enhanced tumor growth inhibition in mice bearing CCRF-CEM xenograft tumors, while causing little side effects, and improved the survival rate of CCRF-CEM tumor-bearing mice in vivo. Therefore, this new self-assembling small molecular prodrug equipped with Sgc8 targeting function is a potential treatment for the targeted therapy of acute lymphoblastic leukemia.

Graphical abstract: Sgc8 aptamer targeted glutathione-responsive nanoassemblies containing Ara-C prodrug for the treatment of acute lymphoblastic leukemia

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Article information


Submitted
27 Aug 2019
Accepted
11 Nov 2019
First published
11 Nov 2019

Nanoscale, 2019,11, 23000-23012
Article type
Paper

Sgc8 aptamer targeted glutathione-responsive nanoassemblies containing Ara-C prodrug for the treatment of acute lymphoblastic leukemia

Z. Fang, X. Wang, Y. Sun, R. Fan, Z. Liu, R. Guo and D. Xie, Nanoscale, 2019, 11, 23000
DOI: 10.1039/C9NR07391D

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