Detection Of Ovarian Cancer Cells Research Articles

Design and application of prodrug fluorescent probes for the detection of ovarian cancer cells and release of anticancer drug

Ovarian cancer is a gynecologic malignancy with high mortality. The main reason is that it is detected at an advanced stage due to a lack of early diagnosis and treatment. Therefore, it is of great interest to develop a chemical tool that can visualize ovarian cancer cells in real-time and eliminate them. Unfortunately, probes that can simultaneously monitor both modes of action for the diagnosis and treatment of ovarian cancer have not been developed. Here, we designed a novel prodrug fluorescent probe (YW-OAc) that not only visually tracks cancer cells but also enables the on-demand delivery of chemotherapeutic agents. By β-Gal-mediated glycosidic bond hydrolysis, the fluorescent signal changed from blue to green (signal 1), enabling visual tracking of ovarian cancer cells. Subsequently, the identified cancer cells were subjected to precise light irradiation to induce anticancer drug release accompanied by a fluorescence transition from green to blue (signal 2), enabling real-time information on drug release. Thus, the prodrug fluorescent probe YW-OAc provides comprehensive two-step monitoring during cancer cell recognition and clearance. Notably, YW-OAc exhibited high affinity (Km = 3.74 μM), high selectivity, and low detection limit for β-Gal (0.0035 U/mL). We also demonstrated that YW-OAc can visually trace endogenous β-Gal in different cells and exhibit high phototoxicity in ovarian cancer cells. We hope that the prodrug fluorescent probe YW-OAc, can be used as an effective tool for biomedical diagnosis and treatment.

Role of Defects of Carbon Nanomaterials in the Detection of Ovarian Cancer Cells in Label-Free Electrochemical Immunosensors.

Developing label-free immunosensors to detect ovarian cancer (OC) by cancer antigen (CA125) is essential to improving diagnosis and protecting women from life-threatening diseases. Four types of carbon nanomaterials, such as multi-wall carbon nanotubes (MWCNTs), vapor-grown carbon fiber (VGCFs), graphite KS4, and carbon black super P (SP), have been treated with acids to prepare a carbon nanomaterial/gold (Au) nanocomposite. The AuNPs@carbon nanocomposite was electrochemically deposited on a glassy carbon electrode (GCE) to serve as a substrate to fabricate a label-free immunosensor for the detection of CA125. Among the four AuNPs@carbon composite, the AuNPs@MWCNTs-based sensor exhibited a high sensitivity of 0.001 µg/mL for the biomarker CA125 through the square wave voltammetry (SWV) technique. The high conductivity and surface area of MWCNTs supported the immobilization of AuNPs. Moreover, the carboxylic (COO-) functional groups in MWCNT improved to a higher quantity after the acid treatment, which served as an excellent support for the fabrication of electrochemical biosensors. The present method aims to explore an environmentally friendly synthesis of a layer-by-layer (LBL) assembly of AuNPs@carbon nanomaterials electrochemical immunoassay to CA125 in a clinical diagnosis at a low cost and proved feasible for point-of-care diagnosis.

Graphene-Based Biosensors with High Sensitivity for Detection of Ovarian Cancer Cells

Ovarian cancer has the highest mortality rate in the world. Therefore, it is urgent but still challenging to develop an efficient circulating tumor cell (CTC) detection method to sensitively detect ovarian cancer. To address such issues, herein, for the first time, we present a novel CTC detection method for ovarian cancer cells by designing sensitive and rapid graphene-based biosensors. This graphene-based sensor, consisting of a cell pool and two electrodes, can be prepared by a conventional chip fabrication process. It demonstrates high-sensitivity detection even for several ovarian cancer cells by comparing the electrical signal before and after adding cell solution. Moreover, the graphene-based biosensors can perform rapid detection with good repeatability. This suggests that this novel method is possible to use for the early detection of ovarian cancer with very low CTC cell concentration. This work provides a novel and quick strategy to detect ovarian cancer and further judge or predict the risk of the transfer of ovarian cancer.

Dual-Stimuli-Responsive Probes for Detection of Ovarian Cancer Cells and Quantification of Both pH and Enzyme Activity

Abstract Many physiological processes involve multiple coordinated chemical and/or biological events. Therefore, it is considered urgent to develop dual-responsive probes for a more comprehensive understanding of the synergistic effects between multiple analytes in complex cellular environments. In this study, we developed a dual-responsive probe βgal-BP-PMB (β-galactosyl–3,3′-dihydroxy-2,2′-bipyridyl–p-methoxybenzyl), the photoluminescence of which can be activated by β-galactosidase (β-gal) and acidic conditions. The overexpression of β-gal is an important feature of senescent and ovarian cancer cells. Single-input activatable probes for detecting β-gal activity in ovarian cancer cells can induce a false positive response from senescent cells. Because the lysosomal pH in senescent cells is increased, probe βgal-BP-PMB can be specifically activated in ovarian cancer cells, but silenced in senescent cells. Probe βgal-BP-PMB has a small molecular size, high sensitivity towards targeted stimuli and unique ratiometric properties, thereby enabling the quantification of both pH and enzyme activity. Such dual-responsive probes could earn a unique place in the field of bioimaging, where multiple analytes should be accurately and simultaneously monitored.

Automatic removal of phase aberration in holographic microscopy for drug sensitivity detection of ovarian cancer cells

Real-time and long-term monitoring of the morphological changes of cells in biomedical science is highly desired. Quantitative phase imaging (QPI) obtained by various interferometric methods is the ideal tool for monitoring such processes as it allows to get quantitative information and thus assessing the right response on cell behaviors. Among QPI, digital holography (DH) in microscope configuration is a powerful tool as it is tolerant versus defocusing and for this reason is able to compensate for eventual defocusing effect during long time-lapse recording. Moreover, DH dynamic phase imaging for biological specimens has several advantages, namely non-invasive, label-free, and high-resolution. However, in DH, one of the main limitations is due to the need compensate aberrations due to the optical components in the object beam. In fact, the image of the object is inevitably embedded in aberrations due to the microscope objective (MO) and other optical components in the optical setup. Here, we propose an automatic and robust phase aberration compensation method based on a synthetic difference (SD) image process. The method is able to detect automatically object-free regions. From such regions, hologram’s aberrations can be accurately evaluated and cleaned up in the final QPI maps. Thanks to our method, temporal evolutions of cell morphological parameters were quantitatively analyzed, hence helping in studying the drug sensitivity of ovarian cancer cells. The experimental results demonstrated that the proposed method could robustly separate the object-free region from the distorted phase image and automatically compensate the total aberrations without any manual interventions, extra components, prior knowledge of the object, and optical setup.

Folic acid conjugated magnetic iron oxide nanoparticles for nondestructive separation and detection of ovarian cancer cells from whole blood.

Because of the lack of early screening strategies, ovarian cancer is the most deadly cause of gynecologic malignancies. This paper describes an effective method for the separation and detection of ovarian cancer cells from female whole blood, using folic acid (FA) conjugated magnetic iron oxide nanoparticles (IO-FA nanoparticles). The IO nanoparticles were synthesized by thermal decomposition and then covalently conjugated with FA. The IO-FA nanoparticles were stably attached to the surface of ovarian cancer cells by coupling to the over-expressed folate receptor (FR), thereby making the cells magnetic. These "magnetic cells" were separated from the complex blood matrix without destruction under a magnetic field. The separation efficiency was as high as 61.3% when the abundance of spiked ovarian cancer SKOV3 cells was as low as 5 × 10(-5)%. We also successfully detected five (5) out of ten (10) metastatic ovarian cancer patients' whole blood. This study suggested the feasibility of early detecting of metastatic ovarian cancer cells, which may potentially improve the ovarian cancers patients' overall survival rate for clinical applications.

A DNA methylation assay for detection of ovarian cancer cells using a HpaII/MspI digestion-based PCR assay in an integrated microfluidic system

Early and accurate diagnosis of cancer plays a very important role in favorable clinical outcomes. DNA methylation of tumor suppressor genes has been recognized as a diagnostic biomarker for early carcinogenesis. The presence of 5-methylcytosine in the CpG islands in the promoter region of a tumor suppressor gene is an important indicator of DNA methylation. However, the standard detection assay utilizing a bisulfite treatment and HpaII/MspI endonuclease digestion is a tedious and lengthy process and requires a relatively large amount of DNA for testing. In this study, the methylated DNAs of various tumor suppressor genes, HAAO, HOXA9 and SFRP5, were chosen as candidates for detection of ovarian cancer cells. The entire experimental process for the DNA methylation assay, including target DNA isolation, HpaII/MspI endonuclease digestion, and nucleic acid amplification has been realized in an integrated microfluidic system. The limit of detection using this developed system has been experimentally determined to be 102 cells/reaction. The entire process from sample loading to analysis of the results only took 3 h which is much faster than the existing protocols. Different sources of biosamples, such as cells, ascites and serums, could be detected with the methylated DNA, indicating that this developed microfluidic system could be adapted for clinical use. Thus, this developed microsystem may be a promising platform for the rapid and early diagnosis of cancers.

Early Detection of Ovarian Cancer Cells using Silica Nanowires and CA125 Biomarkers

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