Diketopyrrolopyrrole-based fluorescence probes for the imaging of lysosomal Zn2+ and identification of prostate cancer in human tissue.
Chenchen DuShibo FuXiaohua WangAdam C SedgwickWei ZhenMinjie LiXinqiang LiJuan ZhouZhong WangHongyu WangJonathan L SesslerPublished in: Chemical science (2019)
A series of diketopyrrolopyrrole-based fluorescent probes (DPP-C2, LysoDPP-C2, LysoDPP-C3, and LysoDPP-C4) have been developed for the detection of low pH and Zn2+ in an AND logic fashion. The chelation of Zn2+ or the protonation of a morpholine moiety within these probes results in a partial increase in the fluorescence intensity, an effect ascribed to suppression of one possible photo-induced electron transfer (PET) pathway. In contrast, a large increase in the observed fluorescence intensity is observed at low pH and in the presence of Zn2+; this is rationalized in terms of both possible PET pathways within the probes being blocked. Job plots, fluorescence titration curves, and isothermal titration calorimetry proved consistent with a 1 : 1 Zn2+ complexation stoichiometry. Each probe demonstrated an excellent selectivity towards Zn2+ and the resulting Zn2+ complexes demonstrated pH sensitivity over the 3.5-9 pH range. Fluorescence imaging experiments confirmed that LysoDPP-C4 was capable of imaging lysosomal Zn2+ in live cells. Little evidence of cytotoxicity was seen. LysoDPP-C4 was successfully applied to the bioimaging of nude mice, wherein it was shown capable of imaging the prostate. Histological studies using a human sample revealed that LysoDPP-C4 can discriminate cancerous prostate tissue from healthy prostate tissue.
Keyphrases
- fluorescence imaging
- prostate cancer
- single molecule
- heavy metals
- living cells
- small molecule
- photodynamic therapy
- high resolution
- endothelial cells
- electron transfer
- fluorescent probe
- quantum dots
- induced apoptosis
- computed tomography
- magnetic resonance
- high intensity
- oxidative stress
- single cell
- risk assessment
- metabolic syndrome
- nucleic acid
- skeletal muscle
- high glucose
- positron emission tomography
- diabetic rats
- high fat diet induced
- loop mediated isothermal amplification