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

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