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Enhanced Antitumor Efficacy by a Cascade of Reactive Oxygen Species Generation and Drug Release
Author(s) -
Wang Sheng,
Yu Guocan,
Wang Zhantong,
Jacobson Orit,
Lin LiSen,
Yang Weijing,
Deng Hongzhang,
He Zhimei,
Liu Yuan,
Chen ZhiYi,
Chen Xiaoyuan
Publication year - 2019
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.201908997
Subject(s) - reactive oxygen species , hydrogen peroxide , nanomedicine , doxorubicin , chemistry , radical , drug , linker , pharmacology , combinatorial chemistry , chemotherapy , biochemistry , nanotechnology , materials science , nanoparticle , medicine , computer science , operating system , surgery
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 β‐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.