A Fluorescent Furan-based Probe with Protected Functional Groups for Highly Selective and Non-Toxic Imaging of HT-29 Cancer Cells and 4T1 Tumors.

Most of the previously reported fluorescent organic probes for cancer cell and tumor imaging have significant limitations including chemical toxicity, structural instability, low Stokes shift value, and the inability for selective accumulations in tumors during in vivo imaging. To overcome the mentioned challenges, we synthesized the fluorescent probes with protected polar functional groups to enhance the non-toxicity nature and increase the selectivity toward tumors. In addition, the structural rigidity of the fluorescent probes was increased by embedding aromatic rings in the probe structure. This issue enables us to obtain ultrabright cell images due to enhanced fluorescence quantum yield (ΦFL) values. After synthesis and spectral characterizations, the applicability of two furan-based and imidazole-based fluorescent probes ( abbreviated as DCPEF and DBPPI, respectively) was investigated for ultrabright in vitro and in vivo imaging of cancer cells. The probe DCPEF shows the ΦFL value of 0.946 and the Stocks shift of 86 nm. In addition, probe DBPPI offers the ΦFL value of 0.400 and a Stocks shift of 150 nm. The MTT colorimetric cytotoxicity assay showed that probe DCPEF has minimal effects against HT-29 (cancer) and Vero (normal) cells. The probe DCPEF produced ultrabright fluorescence images from HT-29 cells. In addition, in vivo imaging of cancer cells showed that probe DCPEF selectively accumulates in the 4T1 tumor in mice. The spectral and chemical stability, minimal cytotoxicity, significant Stokes shift, and high degree of selectivity for tumor cells during in vivo imaging make DCPEF an appropriate candidate to be used as a standard probe for cancer cell imaging.

Synthesis and application of the fluorescent furan and imidazole probes for selective in vivo and in vitro cancer cell imaging.

Development of imaging probes for identification of tumors in the early stages of growth can significantly reduce the tumor-related health hazards and improve our capacity for treatment of cancer. In this work, three different furan and imidazole fluorescent derivatives abbreviated as Cyclo X, SAC and SNO are introduced for in vivo and in vitro imaging of cancer cells. The fluorescence quantum yield values were 0.226, 0.400 and 0.479 for Cyclo X, SAC and SNO, respectively. The excitation and emission wavelengths of maximum intensity were (360, 452), (350, 428) and (350, 432) nm for Cyclo X, SAC and SNO, respectively. The MTT reduction assay was used to estimate the cytotoxic activity of the proposed derivatives against HT-29 (cancer) and Vero (normal) cell lines. Cyclo X showed no cytotoxic effect, while SAC and SNO showed significantly higher cytotoxicity against the tested cell lines than cisplatin as a well-known anticancer drug. In vitro fluorescence microscopic images obtained using HT-29 cells showed that Cyclo X produced very bright images. The in vivo cancer cell imaging using 4T1 tumor-bearing mice revealed that Cyclo X is selectively accumulated in the tumor without distribution in the mice body organs. The spectral and structural stability, large Stokes shift, non-cytotoxicity and high level of selectivity for in vivo imaging are properties that make Cyclo X a suitable candidate to be used for long-term monitoring of cancer cells.