Tumor‐Microenvironment‐Responsive Cascade Reactions by a Cobalt‐Single‐Atom Nanozyme for Synergistic Nanocatalytic Chemotherapy

Abstract

Nanocatalytic therapy, involving the nanozyme-triggered production of reactive oxygen species (ROS) in the tumor microenvironment (TME), has demonstrated potential in tumor therapy, but nanozymes still face challenges of activity and specificity that compromise the therapeutic efficacy. Herein, we report a strategy based on a single-atom nanozyme to initiate cascade enzymatic reactions in the TME for tumorspecific treatment. The cobalt-single-atom nanozyme, with CoÀ N coordination on N-doped porous carbon (Co-SAs@NC), displays catalase-like activity that decomposes cellular endogenous H 2 O 2 to produce O 2 , and subsequent oxidase-like activity that converts O 2 into cytotoxic superoxide radicals to efficiently kill tumor cells. By incorporation with doxorubicin, the therapy achieves a significantly enhanced antitumor effect in vivo. Our findings show that cascade TME-specific catalytic therapy combined with chemotherapy is a promising strategy for efficient tumor therapy.

Ferroptosis: challenges and opportunities for nanomaterials in cancer therapy

“…Given the significant differences in ROS levels between normal and tumor tissues [ 130 , 131 ], some ROS-responsive nanosystems of ferroptosis inducers have gradually been developed for tumor therapy by introducing ROS-sensitive chemical bonds [ 132 , 133 ]. Specifically, ROS-responsive delivery systems induce ferroptosis by loading small-molecule inducers of ferroptosis, which improves their aqueous solubility and targeting properties, enabling precise drug release in the tumor environment [ 114 ].…”

Mo@ZIF-8 nanozyme preparation and its antibacterial property evaluation

“…Currently, types of materials, such as metals ( Gu et al, 2020 ; Tian et al, 2021 ), metal oxides ( Li et al, 2018 ; Dong et al, 2022 ), carbon materials ( Bi et al, 2022 ), single-atom materials ( Cai et al, 2022 ) and MXenes ( Yu et al, 2022b ), have been verified to have peroxidase (POD)-like activity when they are fabricated to nanoscale. These nanozymes can convert H 2 O 2 into OH radicals to effectively kill bacteria.…”

A Single‐Atom Nanozyme Cascade for Selective Tumor‐Microenvironment‐Responsive Nanocatalytic Therapy

“…Further, the cytotoxicity induced by O 2 *À generation has been confirmed from the intense fluorescence observed on incubation of cells with Co-SAs@NC at pH 6.0 using 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA) (Figure 2B). The flow cytometry results indicated early or late apoptosis (83.1 %) of cells while no apparent cell apoptosis [21] Considering future clinical trials, it is worth screening the biodistribution of the catalyst before assessing the in vivo behavior. Hence, Co-SAs@NC showed a good distribution in the liver and spleen after 24 hours of i. v. injection.…”

“…They have designed atomically dispersed cobalt atoms coordinated by nitrogen atoms of N-doped porous carbon (Co-SAs@NC) which exhibits catalase and oxidase-like behavior. [21] This dual nanozyme activity of Co-SAs@NC has been explored for the cascade catalysis to efficiently induce tumor cell apoptosis. The Co-SAs@NC displayed catalase-like activity at pH 6 species.…”

“…The inductively coupled plasma mass spectrometry (ICP-MS) data showed a Co mass percentage of 0.506 wt %. [21] The enzymatic behavior, i. e. catalase and oxidase mimicking activities (Figure 2A), and the detection of individual ROS are thoroughly investigated by the authors using ESR. The catalaselike behavior was monitored under N 2 atmosphere using a trap 3-carbamoyl-2,2,5,5-tetramethyl-3-pyrrolin-1-yloxy (CTPO) that captured O 2 *À generated continuously by the catalyst.…”