Development of pH/Glutathione-Responsive Theranostic Agents Activated by Glutathione S-Transferase π for Human Colon Cancer.
Ji LiuXin LiuJianqiang QianChi MengPeng ZhuJiaying HangYaling WangBiao XiongXiaodong QiuWeizhong ZhuYuming YangYanan ZhangYong LingPublished in: Journal of medicinal chemistry (2020)
Two novel theranostic agents HJTA and HJTB have been designed and synthesized by covalently linking a β-carboline derivative, with antitumor activities and pH-responsive fluorescence, with a 2-exomethylenecyclohexanone moiety, which can be activated by the tumor-targeting glutathione (GSH)/glutathione S-transferase π (GSTπ). These agents showed pH- and GSH-dual-responsive fluorescence in tumor cells but not in normal cells. Importantly, HJTA selectively illuminated tumor tissue for up to 7 h and generated precise visualization of orthotopic colonic tumors through the blood circulation system in intraoperative mice. Furthermore, HJTA exhibited potent and selective antiproliferative activities and colonic tumor inhibition in mice. Finally, HJTA induced great cancer cell apoptosis and autophagy by regulating the expression of apoptotic and autophagic proteins. Therefore, this pH/GSH-dual-responsive fluorescent probe with cancer-targeting therapeutic activity provides a novel tool for precise diagnosis and tumor treatment, therefore broadening the impact of multifunctional agents as theranostic precision medicines.
Keyphrases
- fluorescent probe
- cancer therapy
- cell death
- living cells
- photodynamic therapy
- papillary thyroid
- drug delivery
- endothelial cells
- oxidative stress
- high fat diet induced
- induced apoptosis
- cell cycle arrest
- single molecule
- type diabetes
- endoplasmic reticulum stress
- poor prognosis
- squamous cell carcinoma
- fluorescence imaging
- cell proliferation
- adipose tissue
- long non coding rna
- anti inflammatory
- high glucose
- wild type
- iron oxide