Blocking Metallothionein-2 Expression by Copper-Doped Carbon Dots Induces Cellular Antioxidant System Collapse for Antitumor Therapy.
Kexuan LiuXinchen LiuLinlin WenWenhao ZhaiRongrong YeBoya ZhangWangni XieXue ZhangWenbing ZhangHaiqiu LiJiaqi XuLei HuangHuan WangDaowei LiHongchen SunPublished in: Nano letters (2024)
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.
Keyphrases
- poor prognosis
- quantum dots
- oxidative stress
- anti inflammatory
- long non coding rna
- reactive oxygen species
- visible light
- dna damage
- metal organic framework
- stem cells
- ischemia reperfusion injury
- diabetic rats
- cognitive decline
- type diabetes
- aqueous solution
- gene expression
- high fat diet
- cell proliferation
- squamous cell carcinoma
- young adults
- cancer therapy
- induced apoptosis
- rna seq
- papillary thyroid
- small molecule
- metabolic syndrome
- mesenchymal stem cells
- endoplasmic reticulum stress
- heat stress