Premium
Self‐Assembled Single‐Site Nanozyme for Tumor‐Specific Amplified Cascade Enzymatic Therapy
Author(s) -
Wang Dongdong,
Wu Huihui,
Wang Changlai,
Gu Long,
Chen Hongzhong,
Jana Deblin,
Feng Lili,
Liu Jiawei,
Wang Xueying,
Xu Pengping,
Guo Zhen,
Chen Qianwang,
Zhao Yanli
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202008868
Subject(s) - chemistry , reactive oxygen species , enzyme , glutathione , peroxidase , intracellular , tumor microenvironment , radical , biophysics , in vivo , biochemistry , tumor cells , cancer research , biology , microbiology and biotechnology
Nanomaterials with enzyme‐mimicking activity (nanozymes) show potential for therapeutic interventions. However, it remains a formidable challenge to selectively kill tumor cells through enzymatic reactions, while leaving normal cells unharmed. Herein, we present a new strategy based on a single‐site cascade enzymatic reaction for tumor‐specific therapy that avoids off‐target toxicity to normal tissues. A copper hexacyanoferrate (Cu‐HCF) nanozyme with active single‐site copper exhibited cascade enzymatic activity within the tumor microenvironment: Tumor‐specific glutathione oxidase activity by the Cu‐HCF single‐site nanozymes (SSNEs) led to the depletion of intracellular glutathione and the conversion of single‐site Cu II species into Cu I for subsequent amplified peroxidase activity through a Fenton‐type Harber–Weiss reaction. In this way, abundant highly toxic hydroxyl radicals were generated for tumor cell apoptosis. The results show that SSNEs could amplify the tumor‐killing efficacy of reactive oxygen species and suppress tumor growth in vivo.