Enhanced Chemodynamic Therapy by Cu–Fe Peroxide Nanoparticles: Tumor Microenvironment-Mediated Synergistic Fenton Reaction

Abstract

An urgent need in chemodynamic therapy (CDT) is to achieve high Fenton catalytic efficiency at small doses of CDT agents. However, simple general promotion of the Fenton reaction increases the risk of damaging normal cells along with the cancer cells. Therefore, a tailored strategy to selectively enhance the Fenton reactivity in tumors, for example, by taking advantage of the characteristics of the tumor microenvironment (TME), is in high demand. Herein, a heterogeneous CDT system based on copper−iron peroxide nanoparticles (CFp NPs) is designed for TME-mediated synergistic therapy. CFp NPs degrade under the mildly acidic conditions of TME, selfsupply H 2 O 2 , and the released Cu and Fe ions, with their larger portions at lower oxidation states, cooperatively facilitate hydroxyl radical production through a highly efficient catalytic loop to achieve an excellent tumor therapeutic efficacy. This is distinct from previous heterogeneous CDT systems in that the synergism is closely coupled with the Cu + -assisted conversion of Fe 3+ to Fe 2+ rather than their independent actions. As a result, almost complete ablation of tumors at a minimal treatment dose is demonstrated without the aid of any other therapeutic modality. Furthermore, CFp NPs generate O 2 during the catalysis and exhibit a TME-responsive T 1 magnetic resonance imaging contrast enhancement, which are useful for alleviating hypoxia and in vivo monitoring of tumors, respectively.

Cancer Cell Membrane Biomimetic Mesoporous Nanozyme System with Efficient ROS Generation for Antitumor Chemoresistance

“…Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Ki-67 staining of tumor tissues from all groups are shown in Figure 5(g); the CSD group showed a large amount of tumor cell apoptosis and lower cell proliferation effect. ROS can destroy the active components of tumor cells, causing damage to their cell membranes, nucleic acids, proteins, etc., eventually leading to cell death [40,41]. TME stimulated by DDP upregulates H 2 O 2 levels, thereby promoting the ROS content catalyzed by CSD.…”

Application and prospect of ROS-related nanomaterials for orthopaedic related diseases treatment

“…According to the related theory of chemodynamic therapy, nanoparticles that usually activate chemodynamic therapy include necessary metal elements, such as Fe, Cu, etc. ( Wu et al, 2019 ; Koo et al, 2022 ). Chemodynamic therapy is often used in conjunction with other therapies such as photothermal, photodynamic, or immunotherapy to achieve synergistic effects.…”

Iron oxide@chlorophyll clustered nanoparticles eliminate bladder cancer by photodynamic immunotherapy-initiated ferroptosis and immunostimulation

“…The integration of peroxidase mimics with transition metal ions can generate highly reactive hydroxyl radicals and trigger a decrease in intracellular GSH levels in other malignancies by Fenton-like reactions [17][18][19]. However, the use of ferroptosis-related CDT relying on the metal-dependent reaction [14][15][16] has commonly shown limited efficiency due to the consumption of H 2 O 2 in the tumor site, with a high [oxidized metal ion]/[reduced metal ion] ratio [29,30] that decreases the catalytic rate and results in unsatisfactory efficacy in eradicating the primary tumor. In addition, the highly efficient delivery and accumulation of metal-based species in malignant lesions through blood vessels was the first goal of specific CDT induction [31].…”