Therapeutic Frontiers in Nanozyme-Based Cancer Treatment: Advances, Challenges, and Future Directions

Abstract

Nanozymes, artificial nanomaterials mimicking enzyme activity, are at the forefront of innovative cancer therapies, particularly in chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT). Their capacity to selectively generate reactive oxygen species under tumor-specific conditions, including low pH and high H₂O₂ levels, facilitates targeted induction of cancer cell death while minimizing damage to healthy tissues. When integrated with PDT or PTT, nanozymes enhance oxidative stress and promote immunogenic cell death, further amplifying anti-tumor immune responses. Recent advances in single-atom nanozymes and intelligent nanozymes have shown promise in overcoming therapeutic limitations, such as tumor hypoxia and immune suppression while modulating the tumor microenvironment to boost treatment efficacy. Additionally, ongoing preclinical and clinical evaluations highlight the potential of nanozymes to synergistically enhance immunotherapy outcomes. Their advantages over traditional enzymes, such as stability, tunability, cost-effectiveness, and the ability to maintain catalytic activity in hostile environments, position nanozymes as transformative agents in cancer therapy. However, their clinical translation faces significant challenges, including biocompatibility concerns, delivery inefficiencies to tumor sites, and stringent regulatory hurdles, which require comprehensive research and innovative solutions to address. Despite these limitations, advancements in nanozyme design and functionalization continue to pave the way for more effective and safer applications in cancer therapy which will be discussed in detail in this review.