Tumor Microenvironment Cascade-Responsive Nanodrug with Self-Targeting Activation and ROS Regeneration for Synergistic O
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ARTICLE
Cite as Nano-Micro Lett. (2020) 12:182 Received: 11 May 2020 Accepted: 29 June 2020 © The Author(s) 2020
https://doi.org/10.1007/s40820-020-00492-4
Tumor Microenvironment Cascade‑Responsive Nanodrug with Self‑Targeting Activation and ROS Regeneration for Synergistic Oxidation‑Chemotherapy Yang Li1,2,3, Jinyan Lin2, Peiyuan Wang1,2,3, Qiang Luo1,2,3, Fukai Zhu4, Yun Zhang1,3, Zhenqing Hou4, Xiaolong Liu1,2,3 *, Jingfeng Liu1,2,3 * Yang Li and Jinyan Lin have contributed equally to this work. * Xiaolong Liu, [email protected]; Jingfeng Liu, [email protected] CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
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The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People’s Republic of China Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy of Sciences, Xiamen 361024, People’s Republic of China College of Materials, Xiamen University, Xiamen 361005, People’s Republic of China
HIGHLIGHTS • A pH/ROS cascade-responsive carrier-free nanodrug with self-targeting activation and ROS regeneration abilities. • On-demand release of VES in response to intracellular ROS to accelerate drug release via positive-feedback loop. • Highly synergistic therapeutic efficiency via orchestrated cooperation of oxidation-chemotherapy.
ABSTRACT Carrier-free nanodrug with exceptionally high drug payload has attracted
increasing attentions. Herein, we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop. The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate (MTX) self-assembles into nanoparticles (VSeM); decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time. Upon reaching tumor sites, acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake. Afterward, the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release; then the released VES could produce extra ROS to accelerate the collapse of VSeM. Finally, the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy. Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment. KEYWORDS Targeting activation; Positive-feedback loop; Circular amplification of ROS; Vitamin E nanodrug; Synergistic oxidationchemotherapy
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1 Introduction Integrating advantages of carrier-free nanodrug (e.g., exceptionally high drug payload and
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