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.e., (FeCoNiCuZnAl)Ox (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 NOx-like activity, which can disturb the tumor energy metabolism homeostasis, leading to cell apoptosis. Furthermore, in vitro and in vivo 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.