A specific environment-sensitive near-infrared fluorescent turn-on probe for synergistic enhancement of anticancer activity of a chemo-drug.
Jun LiZhipeng ZhuShaoqin RongHeran LiYuenan GuoQiang XueDan DingPublished in: Biomaterials science (2018)
Chemotherapy is one of the main categories of clinical cancer treatment. One of the hindrances of a popularly used chemo-drug doxorubicin (DOX) is that some types of cancer cells are or become insensitive/resistant to DOX. In this work, we report a near-infrared (NIR) fluorescent turn-on probe DBT-2EEGYLFFVFER by conjugation of an environment-sensitive fluorophore DBT with human epidermal growth factor receptor 2 (HER2) specific binding peptides. Besides the NIR fluorescence turn-on signature, DBT-2EEGYLFFVFER also has activatable capability of reactive oxygen species (ROS) generation. DBT-2EEGYLFFVFER is weakly fluorescent in aqueous solution and hardly produces ROS under white light irradiation. However, both the NIR fluorescence and ROS production ability can be switched on when DBT-2EEGYLFFVFER binds to HER2 proteins overexpressed in cancer cells. Besides specific visualization of HER2-expressed cancer cells, DBT-2EEGYLFFVFER upon exposure to light is able to effectively increase the intracellular ROS level and offer an intracellular oxidative microenvironment, which does not cause the death of cancer cells, but greatly and synergistically boosts the cytotoxicity of DOX against HER2-expressed cancer cells with a supra-additive effect of "0 + 1 > 1".
Keyphrases
- living cells
- fluorescent probe
- reactive oxygen species
- epidermal growth factor receptor
- cancer therapy
- photodynamic therapy
- single molecule
- aqueous solution
- cell death
- dna damage
- locally advanced
- endothelial cells
- tyrosine kinase
- quantum dots
- advanced non small cell lung cancer
- stem cells
- squamous cell carcinoma
- fluorescence imaging
- energy transfer
- drug induced
- combination therapy
- binding protein