Layered Double Hydroxide (LDH)-Based Nanotripod for High-Entropydynamic Therapy Associated with Metabolism Homeostasis

Multielemental transition metal compounds represent a class of promising candidates for the biomedical field due to their unique structure and biomedical application potential. However, their synthesis process remains challenging, which was subject to the high-temperature treatment of the multimetallic elements integrated within one system. Herein, for the first time, we have fabricated the nanotripod, <i>i.e.</i>, (FeCoNiCuZnAl)O_<i>x</i> (denoted as HEO) agent, via the structural topotactic transformation of layered double hydroxide (LDH) precursors with the tunable disorder degree, for highly efficient high-entropydynamic therapy associated with metabolism homeostasis. By virtue of this unique high-entropy structure, the outburst reactive oxygen species (ROS) generation can be regulated via turbulence. These unique high-entropy oxides not only presented outstanding ROS generation efficiency but also broke the intracellular metabolic balance cycle (NADH/NAD⁺) by NO<i>_x</i>-like activity, which can disturb the tumor energy metabolism homeostasis, leading to cell apoptosis. Furthermore, <i>in vitro</i> and <i>in vivo</i> experiments both indicate that this agent was a satisfying candidate for magnetic resonance imaging (MRI)-guided therapy. The findings offer a strategy for the development of high-entropydynamic therapy.