Tumor imaging tools with high specificity and sensitivity are needed to aid the boundary recognition in solid tumor diagnosis and surgical resection. In this study, we developed a near infra-red (NIR) probe ( P6 ) for in vitro/in vivo tumor imaging on the basis of the dual strategy of cancer cell targeting and stimulus-dependent activation. The selective imaging capacity towards cancer cells of P6 was thoroughly investigated, and the potential mechanisms of endocytosis were preliminary explored. Methods: GSH-activated biotin labelled NIR probe ( P6 ) was designed, synthesized and characterized. The GSH responsive properties were systematically illustrated through UV-vis, fluorescent tests and LC-MS analysis. In vitro fluorescent imaging of probe P6 was collected in various living cancer cell lines ( i.e. SW480, HGC-27, H460, BxPC-3, KHOS) and normal cell lines ( i.e. BEAS-2B, HLF-1, THP1) under confocal laser scanning microscopy. Probe P6 was further applied to image primary human cancer cells which were freshly isolated from the peritoneal carcinoma and rectal cancer patients. Serial sections of human tumor tissues were collected and sent for H&E (hematoxylin-eosin) staining and P6 imaging. Live fluorescent and photoacoustic imaging were used to investigate the in vivo imaging of P6 in both tumor and normal tissues in HGC-27 and KHOS xenograft model. Results: Probe P6 could be recognized and transported into cancer cells by tumor specific biotin receptors and efficiently be triggered by GSH to release fluorophore 4 . In fact, the cellular uptake of P6 could be partially blocked by the addition of free biotin. Furthermore, probe P6 could image various cancer cell lines, as well as primary cancer cells, exhibiting a ten-fold increase in fluorescence intensity over normal cells. In freshly dissected cancer tissues, P6 fluorescent imaging distinguished the cancerous area under confocal laser scanning microscopy, which was exact the same area as indicated by H&E staining. We also found that P6 exhibited superior selectivity against cancer tissues by local injection. Conclusion: In this study, we developed a dual-modal NIR probe P6 with enhanced cellular uptake into cancer cells and environmental stimulus triggered fluorescence. Our strategy provided a novel insight into the development of imaging tools that could be potentially used for fluorescent image-guided cancer boundary recognition and possibly cancer diagnosis.

A series of 1,4-thiazepin-5(4H)-one derivatives were synthesized via a transition metal-free one-pot Smiles rearrangement process at room temperature. Regioselective seven-membered heterocycles were constructed in good to excellent yields. To gain an in-depth understanding of the S-N type Smiles rearrangement mechanism, a theoretical study was also performed by quantum chemistry calculations.

A series of valepotriate derivatives with novel skeleton were synthesized from commercial available genipin. Among them, 1e exhibited significant anti-proliferation activity against H1975 cells by inducing mitochondrion-mediated apoptosis.

With this research we set out to develop of a number of coumarin-based ‘AND’ logic fluorescence probes that were capable of detecting a chosen analyte in the presence of HCys.

No abstract

Pulmonary fibrosis (PF) is a fatal disease with increasing prevalence. Nonradioactive and noninvasive diagnosis of PF at an early stage can improve the prognosis but represents a daunting challenge. Up-regulation of nitric oxide (NO) is a typical microenvironmental feature of PF. Here, we report a small-molecule probe, PNO1, that can fluorogenically sense this microenvironmental feature for PF diagnosis. We demonstrate that PNO1 fluorescence is 6-fold higher in PF-diseased mice lungs than in normal-control groups. In addition to this in vivo result, PNO1 can also be applied in vitro to detect PF-diseased cells and ex vivo to detect PF-diseased tissues from clinical patients. These results highlight PNO1 as a complement to the traditional immunostaining-based methods for PF detection to facilitate quick screening for anti-PF drug candidates.

No abstract

Fluorescence probes are emerging as appealing tools for tumor imaging, although the discovery of ideal probes with high tumor selectivity and desirable tumor-tonormal contrast remains challenging. There are currently two strategies used for designing tumor-targeted probes. One is employing tumor-targeting agents and the other is tumormicroenvironment-activatable probes. Although these two strategies have been widely explored, there are few reports on the comparison of probe performance designed based on the two strategies. Herein, by targeting somatostatin receptors (SSTR) overexpressed in neuroendocrine tumors with octreotide (OCT), we have designed two probes, with probe P5 being tumor-microenvironment-activatable and P5cc 3 having fluorescence always on. A comparison of their selectivity toward tumor cells over SSTR-expressing normal cells demonstrated that these two probes showed a similar degree of tumor selectivity, whereas the activatable probe P5 showed enhanced tumor-to-normal imaging contrast due to its tumor-microenvironment-activatable fluorescence. Our results consolidate the rationality of either strategy for designing tumor-targeted imaging agents, and highlight the activatable strategy as a feasible way of enhancing tumor-to-normal imaging contrast.