Diketopyrrolopyrrole-based fluorescence probes for the imaging of lysosomal Zn²⁺ and identification of prostate cancer in human tissue.

ABSTRACT: 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.

SUBMITTER: Du C 

PROVIDER: S-EPMC6568042 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature