Safety Landscape of Therapeutic Nanozymes and Future Research Directions

Abstract Oxidative stress and inflammation are at the root of a multitude of diseases. Treatment of these conditions is often necessary but current standard therapies to fight excessive reactive oxygen species (ROS) and inflammation are often ineffective or complicated by substantial safety concerns. Nanozymes are emerging nanomaterials with intrinsic enzyme‐like properties that hold great promise for effective cancer treatment, bacterial elimination, and anti‐inflammatory/anti‐oxidant therapy. While there is rapid progress in tailoring their catalytic activities as evidenced by the recent integration of single‐atom catalysts (SACs) to create next‐generation nanozymes with superior activity, selectivity, and stability, a better understanding and tuning of their safety profile is imperative for successful clinical translation. This review outlines the current applied safety assessment approaches and provides a comprehensive summary of the safety knowledge of therapeutic nanozymes. Overall, nanozymes so far show good in vitro and in vivo biocompatibility despite considerable differences in their composition and enzymatic activities. However, current safety investigations mostly cover a limited set of basic toxicological endpoints, which do not allow for a thorough and deep assessment. Ultimately, remaining research gaps that should be carefully addressed in future studies are highlighted, to optimize the safety profile of therapeutic nanozymes early in their pre‐clinical development.