Redox-Activatable Theranostic Co-Prodrug for Precise Tumor Diagnosis and Selective Combination Chemotherapy.
Jianqiang QianZhongyuan XuChi MengYun LiuHongmei WuYunyun WangJinxian YangHongwei ZhengFansheng RanGong-Qing LiuYong LingPublished in: Journal of medicinal chemistry (2022)
A novel theranostic co-prodrug SCB has been designed by combining a co-prodrug from CDDO-Me and SAHA with a biotin-coupled near-infrared (NIR) probe hemicyanine via redox-responsive linker thiolactate to enhance the tumor theranostic efficacy and reduce the toxic side effects using both active and passive targeting strategies. SCB displayed reactive oxygen species (ROS)- and glutathione (GSH)-dependent release of NIR fluorescence and two parent drugs. Furthermore, the administration of SCB caused selective illumination of the tumor tissues for >24 h, thereby guiding precise removal of a tumor from intraoperative mice. Importantly, SCB exhibited highly efficient tumor inhibition, exerted selective combination therapy through prodrug mode, and minimized the adverse effects. Finally, SCB induced mitochondrial depolarization, DNA damage, and cell apoptosis through ROS generation and downregulation of HDAC6 protein, as verified by H2AX, Bax, cleaved-PARP, and Mcl-1 proteins. Thus, we suggest that SCB can provide a new platform for both precise diagnosis-guided tumor removal and selective combination therapy with high safety.
Keyphrases
- combination therapy
- dna damage
- photodynamic therapy
- reactive oxygen species
- fluorescence imaging
- highly efficient
- oxidative stress
- drug release
- gene expression
- radiation therapy
- cell death
- squamous cell carcinoma
- metabolic syndrome
- skeletal muscle
- type diabetes
- quantum dots
- small molecule
- drug delivery
- binding protein
- single molecule
- rectal cancer
- high fat diet induced
- high glucose