DIG790 is indicated for the treatment of patients with advanced Epithelial Ovarian Cancer.
DiaGyn has developed an ideal treatment strategy for EOC based on nanoparticles technology.
The innovative product comprises 100 nm Mesoporous Silica Nano Particle (MSNP) loaded with the antineoplastic Docetaxel and capped with the cyclic oligosaccharide, Cyclodextrin.
The Cyclodextrin cap linked to the silica particles avoid non-controlled release of chemotherapy from the pores before arrival to the site of action.
DiaGyn’s nanoparticles special design involves a sensitive linker that selectively senses the high levels β-galactosidase and low pH encountered in the surroundings of the EOC cells, releasing the drug to the malignant cells while normal tissue remains largely unaffected.
Recent publications in academic journals have discussed the properties of β-galacatosidase enzyme as a unique biomarker overexpressed in ovarian cancer cells but not in regular cells.
β-Galactosidase as a Unique Marker for Ovarian Cancers
Fluorescence-guided diagnostics is one of the most promising approaches for facile detection of cancer in situ. Here we focus on β-galactosidase, which is overexpressed in primary ovarian cancers, as a molecular target for visualizing peritoneal metastases from ovarian cancers. As existing fluorescence probes are unsuitable, we have designed membrane-permeable HMRef-βGal, in which the optimized intramolecular spirocyclic function affords >1,400-fold fluorescence enhancement on activation. We confirm that HMRef-βGal sensitively detects intracellular β-galactosidase activity in several ovarian cancer lines. In vivo, this probe visualizes metastases as small as <1 mm in diameter in seven mouse models of disseminated human peritoneal ovarian cancer (SHIN3, SKOV3, OVK18, OVCAR3, OVCAR4, OVCAR5 and OVCAR8). Because of its high brightness, real-time detection of metastases with the naked eye is possible. Endoscopic fluorescence detection of metastases is also demonstrated. The results clearly indicate preclinical potential value of the probe for fluorescence-guided diagnosis of peritoneal metastases from ovarian cancers.
Development of a Long-Lived Luminescence Probe Visualizing β-Galactosidase in Ovarian Carcinoma Cells.
β-Galactosidase (β-gal) is an important biomarker for ovarian cancers. In this work, we designed and synthesized a novel iridium(III)-based probe 1 for discriminating ovarian carcinoma cell lines from normal cell lines. The probe could detect β-gal even in the presence of a highly auto-fluorescent background. The probe also showed a good linear response to β-gal between 0 and 30 U/mL, with a detection limit of 0.51 U/mL. Importantly, complex 1 could selectively “light up” ovarian carcinoma cells, while exhibiting negligible luminescence in normal cells. Overall, complex 1 could be potentially used as a useful probe for detecting β-gal expression in the context of ovarian cancer diagnostics.
A lysosome-Targetable Two-Photon Fluorescent Probe for imaging Endogenous β-Galactosidase in Living Ovarian Cancer Cells
The early diagnosis of ovarian cancer plays an important role in the treatment of ovarian cancer. β-Galactosidase (β-gal) which is an overexpressed enzyme in primary ovarian cancer can be employed as a valuable biomarker of ovarian cancer. A fluorescent probe for β-gal detection and imaging is of important significance for the diagnosis of primary ovarian cancer. Toward this goal, we have rationally designed and synthesized a novel two-photon fluorescence probe FC- β gal for monitoring endogenous β-gal in lysosome. The probe FC-βgal showed apparently fluorescence changes from blue to green in response to β-gal by the cleavage of glycosidic bond. 4-Propylmorpholine group endowed the probe with the property of lysosomal targeting. We confirmed that the probe FC-βgal exhibited rapid response, high sensitivity, excellent biocompatibility and favorable performances to β-gal even in the interfering of other biologic substances. In addition, single photon and two-photon confocal imaging experiments indicated that probe FC-βgal displayed a desirable cellular imaging for endogenous β-gal in human ovarian cancer SKOV-3 cells with low cytotoxicity. Moreover, the probe had satisfactory ability to accumulate into lysosomes compared with LysoTracker.