Blocking Metallothionein-2 Expression by Copper-Doped Carbon Dots Induces Cellular Antioxidant System Collapse for
Kexuan Liu1, Xinchen Liu1, Linlin Wen1
1Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, People's Republic of China.
Abstract:
The insufficient antioxidant reserves in tumor cells play a critical role in reactive oxygen species (ROS)-mediated therapeutics. Metallothionein-2 (MT-2), an intracellular cysteine-rich protein renowned for its potent antioxidant properties, is intricately involved in tumor development and correlates with a poor prognosis. Consequently, MT-2 emerges as a promising target for tumor therapy. Herein, we present the development of copper-doped carbon dots (Cu-CDs) to target MT-2 to compromise the delicate antioxidant reserves in tumor cells. These Cu-CDs with high tumor accumulation and prolonged body retention can effectively suppress tumor growth by inducing oxidative stress. Transcriptome sequencing unveils a significant decrease in MT-2 expression within the in vivo tumor samples. Further mechanical investigations demonstrate that the antitumor effect of Cu-CDs is intricately linked to apolipoprotein E (ApoE)-mediated downregulation of MT-2 expression and the collapse of the antioxidant system. The robust antitumor efficacy of Cu-CDs provides invaluable insights into developing MT-2-targeted nanomedicine for cancer therapies.
Insights
Copper-doped carbon dots (Cu-CDs) target metallothionein-2 (MT-2) to deplete tumor antioxidant defenses, effectively inhibiting cancer growth. This novel nanomedicine approach shows promise for MT-2-targeted cancer therapy.
Area of Science:
- Nanomedicine
- Cancer Therapeutics
- Biochemistry
Background:
- Tumor cells' low antioxidant capacity is crucial for reactive oxygen species (ROS)-mediated therapies.
- Metallothionein-2 (MT-2), a potent antioxidant protein, is linked to tumor progression and poor prognosis, making it a therapeutic target.
Purpose of the Study:
- To develop copper-doped carbon dots (Cu-CDs) for targeting MT-2 in tumor cells.
- To investigate the potential of Cu-CDs to compromise tumor antioxidant reserves and inhibit tumor growth.
Main Methods:
- Synthesis and characterization of copper-doped carbon dots (Cu-CDs).
- Evaluation of Cu-CDs' tumor accumulation, retention, and antitumor efficacy in vivo.
- Transcriptome sequencing to analyze MT-2 expression changes.
- Mechanistic studies involving apolipoprotein E (ApoE) and antioxidant system collapse.
Main Results:
- Cu-CDs demonstrated high tumor accumulation and prolonged body retention, effectively suppressing tumor growth via induced oxidative stress.
- Transcriptome sequencing revealed a significant decrease in MT-2 expression in in vivo tumor samples treated with Cu-CDs.
- Antitumor effects were linked to ApoE-mediated downregulation of MT-2 and subsequent collapse of the cellular antioxidant system.
Conclusions:
- Cu-CDs effectively target MT-2, disrupt tumor antioxidant defenses, and exhibit robust antitumor efficacy.
- The findings highlight the potential of MT-2-targeted nanomedicine, specifically Cu-CDs, for developing novel cancer therapies.
