Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 58, Issue 41, Pages 14758-14763Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201908997
Keywords
cancer therapy; drug delivery; Fenton reaction; nanomedicine; prodrugs
Categories
Funding
- National Natural Science Foundation of China [81671707]
- Natural Science Foundation of Guangdong Province [2016A030311054]
- Research Projects of Guangzhou Science Technology and Innovation Commission [201607010201]
- Higher Education Colleges and Universities Innovation Strong School Project [Q17024072]
- Research Fund of National Education Steering Committee for Graduates in Medical Degree [B3-20170302-06]
- Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
- Research Fund for Lin He's Academician Workstation of New Medicine and Clinical Translation
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [ZIAEB000073] Funding Source: NIH RePORTER
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Reactive oxygen species (ROS) can be used not only as a therapeutic agent for chemodynamic therapy (CDT), but also as a stimulus to activate release of antitumor drugs, achieving enhanced efficacy through the combination of CDT and chemotherapy. Here we report a pH/ROS dual-responsive nanomedicine consisting of beta-lapachone (Lap), a pH-responsive polymer, and a ROS-responsive polyprodrug. In the intracellular acidic environment, the nanomedicine can realize pH-triggered disassembly. The released Lap can efficiently generate hydrogen peroxide, which will be further converted into highly toxic hydroxyl radicals via the Fenton reaction. Subsequently, through ROS-induced cleavage of thioketal linker, doxorubicin is released from the polyprodrug. In vivo results indicate that the cascade of ROS generation and antitumor-drug release can effectively inhibit tumor growth. This design of nanomedicine with cascade reactions offers a promising strategy to enhance antitumor efficacy.
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