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A Versatile Nanozyme-Based NADH Circulating Oxidation Reactor for Tumor Therapy through Triple Cellular Metabolism
Ke Liang1,2, Fuchun Nan1,2, Jian Wang1,2
1Key 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.
Abstract:
Nanozyme-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.
Insights
This study introduces a novel nanozyme nanoreactor that oxidizes nicotinamide adenine dinucleotide (NADH) to disrupt tumor cell metabolism. This approach enhances therapeutic efficacy by overcoming substrate limitations and metabolic plasticity in tumors.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Nanozyme-based therapies show promise for cancer treatment by targeting tumor metabolism.
- Current strategies face limitations due to low substrate concentrations and tumor metabolic adaptability.
- Efficient metabolic regulation is crucial for effective tumor therapy.
Purpose of the Study:
- To develop a versatile nanozyme-based nanoreactor for tumor therapy.
- To address the limitations of substrate deficiency and metabolic plasticity in nanozyme-based cancer treatments.
- To create a nanoreactor capable of triple cellular metabolism disruption.
Main Methods:
- Synthesized cobalt-doped hollow carbon spheres (Co-HCS) with NADH oxidase (NOX)-mimicking activity.
- Engineered Co-HCS for substrate-cycle NADH circulating oxidation to overcome deficiency.
- Combined Co-HCS with 2-Deoxy-D-glucose (2-DG) and 6-aminonicotinamide (6-AN) to inhibit glycolysis and pentose phosphate pathway (PPP).
Main Results:
- The designed nanoreactor (Co-HCS/D/A) demonstrated enhanced catalytic efficiency.
- Disruption of tumor cell oxidative phosphorylation (OXPHOS) pathway.
- Effective disruption of tumor metabolic homeostasis through triple pathway inhibition, leading to efficient in vitro and in vivo therapy outcomes.
Conclusions:
- Developed a novel nanozyme-based NADH circulating oxidation nanoreactor for enhanced tumor therapy.
- The nanoreactor effectively disrupts tumor metabolism via triple pathway inhibition, addressing current limitations.
- This strategy offers a promising approach for overcoming challenges in nanozyme-based cancer treatment.
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