Layered double hydroxide-based nanozyme for NO-boost multi-enzyme dynamic therapy with tumor specificity

The development of dual chemodynamic therapy and NO therapy can significantly improve the efficiency of cancer treatment. Therefore, designing a multifunctional agent to take full advantage of them and maximize their therapeutic effect remains a challenging goal. Herein, we have developed a novel LDHzyme by the confinement of L-arginine (L-Arg) on the surface of Mn-LDH nanosheets. The LDHzyme can exhibit multiple enzyme-like catalytic activities, including peroxidase (POD), oxidase (OXD), and nitric oxide synthase (iNOS). Based on these enzyme-mimicking properties, LDHzyme possesses significant catalytic efficiency with a high maximum velocity of 1.41 × 10^-6 M s^-1, which is higher than the majority of other nanozymes. In addition, this LDHzyme can exhibit outstanding NO-enhanced lethality of ROS and further improve its efficacy. The therapeutic effect of LDHzyme has been verified to significantly inhibit tumor growth in HeLa xenograft Balb/c nude mice models, as demonstrated in both in vitro and in vivo models, revealing the promising prospects of NO-enhanced multi-enzyme dynamic therapy (MDT). These results open up an opportunity to enable the utilization of an LDH-based nanozyme as a curative nanosystem to inhibit tumor growth.