Affiliation:
1. Key Laboratory of Photochemical Conversion and Optoelectronic Materials and CityU‐CAS Joint Laboratory of Functional Materials and Devices Technical Institute of Physics and Chemistry Chinese Academy of Sciences Beijing 100049 P. R. China
2. School of Future Technology University of Chinese Academy of Sciences Beijing 100049 China
3. Weiqiao‐UCAS Science and Technology Park Binzhou Institute of Technology Binzhou Shandong 256606 China
Abstract
AbstractNanozyme‐based metabolic regulation triggered by tumor‐specific endogenous stimuli has emerged as a promising therapeutic strategy for tumors. The current efficacy, however, is constrained by the limited concentration of endogenous substrates and the metabolic plasticity of tumors. Consequently, the implementation of efficient metabolic regulation in tumor therapy is urgently needed. Herein, a versatile nanozyme‐based nicotinamide adenine dinucleotide (NADH) circulating oxidation nanoreactor is reported. First, the synthesized cobalt‐doped hollow carbon spheres (Co‐HCS) possess NADH oxidase (NOX)‐mimicking activity for the NADH oxidation to disrupt oxidative phosphorylation (OXPHOS) pathway of tumor cells. Second, the substrate‐cycle manner of Co‐HCS can be used for NADH circulating oxidation to overcome the limitation of substrate deficiency. Finally, 2‐Deoxy‐D‐glucose (2‐DG) and 6‐aminonicotinamide (6‐AN) are introduced to block glycolysis and pentose phosphate pathway (PPP), thus creating a versatile nanozyme‐based NADH circulating oxidation nanoreactor (Co‐HCS/D/A) for tumor therapy through triple cellular metabolism disruption. In vitro and in vivo results demonstrate that the designed nanoreactor not only enhances the catalytic efficiency but also disrupts the tumor metabolic homeostasis, leading to efficient therapy outcome. This study develops a novel NADH circulating oxidation nanoreactor for tumor therapy through triple cellular metabolism disruption, which addresses the limitations of current nanozyme‐based metabolism regulation for tumor therapy.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Subject
Biomaterials,Biotechnology,General Materials Science,General Chemistry