Graphene Quantum Dots Eradicate Resistant and Metastatic Cancer Cells by Enhanced Interfacial Inhibition.
Yan SuKai YeJinyan HuZhenlin ZhangYang WangBijiang GengDengyu PanLongxiang ShenPublished in: Advanced healthcare materials (2024)
Drug-resistant and metastatic cancer cells such as a small population of cancer stem cells (CSCs) play a crucial role in metastasis and relapse. Conventional small-molecule chemotherapeutics, however, are unable to eradicate drug-resistant CSCs owing to limited interface inhibitory effects. Herein, it is reported that enhanced interfacial inhibition leading to eradication of drug-resistant CSCs can be dramatically induced by self-insertion of bioactive graphene quantum dots (GQDs) into DNA major groove (MAG) sites in cancer cells. Since transcription factors regulate gene expression at the MAG site, MAG-targeted GQDs exert greatly enhanced interfacial inhibition, downregulating the expression of a collection of cancer stem genes such as ALDH1, Notch1, and Bmi1. Moreover, the nanoscale interface inhibition mechanism reverses cancer multidrug resistance (MDR) by inhibiting MDR1 gene expression when GQDs are used at a nontoxic concentration (1/4 × half-maximal inhibitory concentration (IC 50 )) as the MDR reverser. Given their high efficacy in interfacial inhibition, CSC-mediated migration, invasion, and metastasis of cancer cells can be substantially blocked by MAG-targeted GQDs, which can also be harnessed to sensitize clinical cytotoxic agents for improved efficacy in combination chemotherapy. These findings elucidate the inhibitory effects of the enhanced nano-bio interface at the MAG site on eradicating CSCs, thus preventing cancer metastasis and recurrence.
Keyphrases
- drug resistant
- multidrug resistant
- cancer stem cells
- acinetobacter baumannii
- gene expression
- quantum dots
- papillary thyroid
- small molecule
- squamous cell
- small cell lung cancer
- molecular dynamics simulations
- ionic liquid
- squamous cell carcinoma
- transcription factor
- poor prognosis
- body mass index
- cell proliferation
- pseudomonas aeruginosa
- lymph node metastasis
- childhood cancer
- mass spectrometry
- helicobacter pylori infection
- young adults
- body composition
- genome wide
- single molecule
- helicobacter pylori
- weight gain
- long non coding rna
- energy transfer
- cystic fibrosis
- resistance training
- cell migration
- anti inflammatory