A pH‐Responsive Polymer‐CeO₂ Hybrid to Catalytically Generate Oxidative Stress for Tumor Therapy

Abstract

effect), a lower pH value, as well as a high level of oxidative stress. [4-9] Especially, the overproduction of reactive oxygen species (ROS) induces a serious oxidative stress, which is strongly implicated to various tumors. [8,9] In addition, a high ROS level is also considered to be an endpoint of the alteration of several important metabolic pathways in tumors. [8-11] Thus, modulation of the intratumor ROS level, either by scavenging ROS or increasing ROS, is a promising approach to anticancer therapy and ROS-related biomedical fields. [10-19] Recently, nanomaterial-enabled biocatalytic chemodynamic therapy has been demonstrated as a promising method for therapeutic intervention in a variety of tumors. [11-16,20] Through this biocatalytic tumor therapy, intratumor H 2 O 2 can be converted into toxic hydroxyl radicals (• OH) with the help of catalysts that can then induce tumor cell apoptosis and death through oxidative damage to various biomacromolecules, including DNA, lipids, and proteins. Nevertheless, the relatively deficient intratumoral H 2 O 2 level significantly lowers the biocatalytic therapeutic efficiency. [21-27] Thus, the focus has been on increasing the intratumoral H 2 O 2 level through oxidization of intratumoral molecules Catalytic generation of reactive oxygen species has been developed as a promising methodology for tumor therapy. Direct O 2 •− production from intratumor oxygen exhibits exceptional tumor therapeutic efficacy. Herein, this therapy strategy is demonstrated by a pH-responsive hybrid of porous CeO 2 nanorods and sodium polystyrene sulfonate that delivers high oxidative activity for O 2 •− generation within acidic tumor microenvironments for chemodynamic therapy and only limited oxidative activity in neutral media to limit damage to healthy organs. The hydrated polymer-nanorod hybrids with large hydrodynamic diameters form nanoreactors that locally trap oxygen and biological substrates inside and improve the charge transfer between the catalysts and substrates in the tumor microenvironment, leading to enhanced catalytic O 2 •− production and consequent oxidation. Together with successful in vitro and in vivo experiments, these data show that the use of hybrids provides a compelling opportunity for the delivery selective chemodynamic tumor therapy.

Chemodynamic Therapy via Fenton and Fenton‐Like Nanomaterials: Strategies and Recent Advances

“…There are also examples that use Ce‐containing nanoagents for CDT. [ 19,345,346 ] For example, Xu et al. designed biocompatible PDA/NH 4 HCO 3 ‐coated and DOX‐loaded hollow CeO 2 NPs (termed PDAC NPs) for the combinational PTT/chemotherapy/CDT against cancer.…”

Nanoscale Cerium Oxide: Synthesis, Biocatalytic Mechanism, and Applications

“…The pH factor plays an important role in the reaction catalyzed by nanoscale cerium oxide. For example, Asati and coworkers [59] found that the simulated oxidase activity of nanoscale cerium oxide is highly dependent on environmental pH, and has the strongest activity in acidic acetate buffer, which can be attributed to the protonation effect of nanoscale cerium oxide at low pH [59,69]. This is based on the fact that nanoscale cerium oxide has strong peroxidase and oxidase activities under acidic conditions and strong SOD and CAT activities under neutral or alkaline conditions [70].…”

Redox Active Cerium Oxide Nanoparticles: Current Status and Burning Issues

“…[20] This ability to oxidize substrates such as 3′,3′,5′,5′-tetramethylbenzidine (TMB), 2,2-azinobis (3-ethylbenzothizoline-6-sulfonic acid) (ABTS), o-phenylenediamine, and dopamine have been used for creating pH-or redox-responsive sensors for cancer detection, [21] dopamine sensing, [22] and even generate oxidative stress for tumor therapy. [23] These oxidative properties (oxidase-like or peroxidase-like) have enabled multiple biomedical applications for nanoceria, [24] dividing the scientific community between its pro-oxidant and antioxidant properties. This is especially important for future biomedical applications of nanoceria wherein only anti-oxidative properties are required.…”