Catalytic nanoparticles have emerged as a promising tool in cancer therapy, particularly through their ability to generate reactive oxygen species (ROS) within tumor microenvironments. These nanoparticles, including platinum (Pt) and cerium oxide (CeO2), exhibit enzyme-mimetic activities that can selectively amplify oxidative stress in cancer cells while minimizing damage to healthy tissues. Their unique catalytic properties allow them to mimic natural enzymes such as catalase and peroxidase, enabling precise control over ROS generation in response to specific tumor conditions.

Platinum-based nanoparticles are widely studied for their peroxidase-like activity, which converts hydrogen peroxide (H2O2) into highly cytotoxic hydroxyl radicals (•OH) under acidic conditions. This property is particularly advantageous in cancer therapy because the tumor microenvironment is often characterized by elevated H2O2 levels and lower pH compared to normal tissues. The peroxidase-like activity of Pt nanoparticles is pH-dependent, with optimal catalytic efficiency observed at pH 4.5–5.5, closely matching the acidic extracellular conditions of many solid tumors. In preclinical studies, Pt nanoparticles have demonstrated significant tumor growth inhibition, with reductions in tumor volume exceeding 70% in murine models following localized ROS generation.

Cerium oxide nanoparticles, on the other hand, exhibit dual enzyme-mimetic behavior, functioning as both catalase and peroxidase mimics depending on the surrounding redox environment. In normal tissues, CeO2 nanoparticles act as catalase mimics, decomposing H2O2 into water and oxygen, thereby protecting healthy cells from oxidative damage. However, in the hypoxic and acidic tumor microenvironment, these nanoparticles switch to peroxidase-like activity, converting H2O2 into •OH radicals that induce cancer cell apoptosis. This redox adaptability makes CeO2 nanoparticles highly selective for tumor tissues. Studies in xenograft models have shown that CeO2 nanoparticles can reduce tumor growth by up to 60% while sparing adjacent normal tissues.

The tumor microenvironment-responsive activation of catalytic nanoparticles is a key mechanism for their selective toxicity. Hypoxia, acidic pH, and overexpressed glutathione (GSH) in tumors create conditions that enhance nanoparticle catalytic activity. For instance, the acidic pH not only boosts peroxidase-like activity but also increases nanoparticle uptake by cancer cells through enhanced permeability and retention (EPR) effects. Additionally, the high GSH levels in tumors can be exploited by nanoparticles that deplete GSH, further amplifying oxidative stress. Preclinical data indicate that combining GSH-depleting agents with catalytic nanoparticles can enhance therapeutic efficacy, with some studies reporting synergistic tumor suppression rates exceeding 80%.

Oxidative stress amplification is achieved through multiple pathways. Catalytic nanoparticles not only directly generate ROS but also disrupt cellular antioxidant defense mechanisms. By depleting GSH and inhibiting antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), these nanoparticles push cancer cells into a state of irreversible oxidative damage. This dual action—ROS generation and antioxidant suppression—creates a feedback loop that sustains high oxidative stress levels, leading to DNA damage, lipid peroxidation, and mitochondrial dysfunction. In vitro studies using human cancer cell lines have demonstrated that catalytic nanoparticles can increase intracellular ROS levels by 3–5 fold within hours of treatment, resulting in significant cytotoxicity.

Preclinical efficacy data support the potential of catalytic nanoparticles in cancer therapy. In murine models of breast cancer, Pt nanoparticles combined with low-dose radiation achieved a 90% reduction in tumor volume compared to radiation alone. Similarly, CeO2 nanoparticles have shown promise in pancreatic cancer models, where they improved survival rates by 40% compared to standard chemotherapy. These results highlight the ability of catalytic nanoparticles to enhance conventional therapies through ROS-mediated mechanisms.

Despite their therapeutic potential, catalytic nanoparticles may pose risks to healthy tissues if not carefully controlled. Off-target ROS generation can lead to unintended oxidative damage in normal cells, particularly in organs with high metabolic activity such as the liver and kidneys. Studies have reported transient increases in liver enzymes and mild inflammatory responses following systemic administration of high nanoparticle doses. However, surface modifications, such as polyethylene glycol (PEG) coating or tumor-targeting ligands, have been shown to reduce off-target effects by improving nanoparticle biodistribution and tumor accumulation.

In summary, catalytic nanoparticles represent a versatile platform for ROS-mediated cancer therapy. Their enzyme-mimetic activities, responsiveness to tumor microenvironments, and ability to amplify oxidative stress make them highly effective against cancer cells while sparing healthy tissues. Preclinical studies demonstrate significant tumor suppression and synergistic effects with existing therapies, though careful design is necessary to minimize side effects. Future research should focus on optimizing nanoparticle formulations for clinical translation, including dose optimization and long-term safety assessments.