Precise Regulation of Enzyme–Nanozyme Cascade Reaction Kinetics by Magnetic Actuation toward Efficient Tumor Therapy
Ye Zhang, Yanyun Wang, Qi Zhou, Xiaoyong Chen, Wangbo Jiao, Galong Li, Mingli Peng, Xiaoli Liu, Yuan He, Haiming Fan
Abstract
Spatiotemporal regulation of multi-enzyme catalysis with stimuli is crucial in nature to meet different metabolic requirements but presents a challenge in artificial cascade systems. Here, we report a strategy for precise and tunable modulation of enzyme–nanozyme cascade reaction kinetics by remote magnetic stimulation. As a proof of concept, glucose oxidase (GOx) was immobilized onto a ferrimagnetic vortex iron oxide nanoring (Fe3O4 NR) functionalized with poly(ethylene glycol) of different molecular weights to construct a series of Fe3O4 NR@GOx with nanometer linking distances. The activities of GOx and the Fe3O4 NR nanozyme in these systems were shown to be differentially stimulated by Fe3O4 NR-mediated local heat in response to an alternating magnetic field (AMF), leading to modulated cascade reaction kinetics in a distance-dependent manner. Compared to the free GOx and Fe3O4 NR mixture, Fe3O4 NR(D2)@GOx with an optimum linking distance of 1 nm exhibits a superior kinetic match between GOx and the Fe3O4 NR nanozyme and over a 400-fold higher cascade activity under AMF exposure. This enables remarkable intracellular reactive oxygen species production and significantly improved tumor inhibition of AMF-stimulated Fe3O4 NR(D2)@GOx in 4T1 tumor-bearing mice. The strategy reported here offers a straightforward new tool for fine-tuning multi-enzyme catalysis at the molecular level using magnetic stimuli and holds great promise for use in a variety of biotechnology and synthetic biology applications.