Peptide-Templated Gold Clusters as Enzyme-Like Catalyst Boost Intracellular Oxidative Pressure and Induce
Ya Zhang1, Xiangchun Zhang2, Qing Yuan3
1Department of Chemistry and Chemical Engineering, Beijing University of Technology, No.100, Pingleyuan, Chaoyang District, Beijing 100124, China. zhangya1@ihep.ac.cn.
Abstract:
Anticancer metallodrugs that aim to physiological characters unique to tumor microenvironment are expected to combat drug tolerance and side-effects. Recently, owing to the fact that reactive oxygen species' is closely related to the development of tumors, people are committed to developing metallodrugs with the capacity of improving the level of reactive oxygen species level toinduce oxidative stress in cancer cells. Herein, we demonstrated that peptide templated gold clusters with atomic precision preferably catalyze the transformation of hydrogen peroxide into superoxide anion in oxidative pressure-type tumor cells. Firstly, we successfully constructed gold clusters by rationally designing peptide sequences which targets integrin ανβ₃ overexpressed on glioblastoma cells. The superoxide anion, radical derived from hydrogen peroxide and catalyzed by gold clusters, was confirmed in vitro under pseudo-physiological conditions. Then, kinetic parameters were evaluated to verify the catalytic properties of gold clusters. Furthermore, these peptide decorated clusters can serve as special enzyme-like catalyst to convert endogenous hydrogen peroxide into superoxide anion, elevated intracellular reactive oxygen species levels, lower mitochondrial membrane potential, damage biomacromolecules, and trigger tumor cell apoptosis consequently.
Insights
Peptide-templated gold clusters generate superoxide from hydrogen peroxide, inducing oxidative stress and apoptosis in glioblastoma cells. This metallodrug approach targets tumor microenvironments to combat cancer drug resistance.
Area of Science:
- Nanotechnology
- Materials Science
- Biomedical Engineering
Background:
- Tumor microenvironments possess unique physiological characteristics that contribute to cancer drug tolerance and side effects.
- Reactive oxygen species (ROS) are closely linked to tumor development, prompting research into metallodrugs that can enhance ROS levels to induce oxidative stress in cancer cells.
Purpose of the Study:
- To develop peptide-templated gold clusters capable of catalyzing the conversion of hydrogen peroxide into superoxide anion within tumor cells.
- To investigate the potential of these gold clusters as an anticancer therapeutic strategy by inducing oxidative stress and apoptosis in glioblastoma cells.
Main Methods:
- Construction of gold clusters using rationally designed peptide sequences targeting integrin αvβ3, which is overexpressed on glioblastoma cells.
- In vitro confirmation of superoxide anion generation from hydrogen peroxide catalyzed by gold clusters under pseudo-physiological conditions.
- Evaluation of kinetic parameters to assess the catalytic properties of the gold clusters and their effect on intracellular ROS levels, mitochondrial membrane potential, and biomacromolecule damage.
Main Results:
- Peptide-templated gold clusters were successfully synthesized and demonstrated preferential catalysis of hydrogen peroxide to superoxide anion in oxidative pressure-type tumor cells.
- The generated superoxide anion was confirmed in vitro, and kinetic studies verified the catalytic efficiency of the gold clusters.
- These clusters effectively elevated intracellular ROS, reduced mitochondrial membrane potential, damaged biomacromolecules, and induced apoptosis in tumor cells.
Conclusions:
- Peptide-templated gold clusters act as enzyme-like catalysts, converting endogenous hydrogen peroxide into superoxide anion to induce targeted oxidative stress in cancer cells.
- This metallodrug approach offers a promising strategy for combating drug tolerance and side effects by exploiting tumor-specific characteristics.
- The findings highlight the potential of atomically precise gold clusters as a novel therapeutic agent for glioblastoma treatment.
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