Applications of Aptamers in the Diagnosis and Treatment of Ovarian Cancer: Progress From 2016 to 2020

Nucleic acid aptamers are short single-stranded DNA or RNA oligonucleotides selected from a random single-stranded nucleic acid library using systematic evolution of ligands by exponential enrichment technology. To allow them to bind to molecular targets with the same specificity and precision as that of antibodies, aptamers are folded into secondary or tertiary structures. However, compared to antibodies, aptamers are not immunogenic and are easier to synthesize. Furthermore, they are chemically modified, which protects them from degradation by nucleases. Hence, due to their stability and favorable targeting ability, aptamers are promising for the diagnosis and treatment of diseases. Ovarian cancer has the worst prognosis among all gynecological diseases and is usually diagnosed at the medium and advanced stages due to its nonspecific symptoms. Relapse is common, even if patients receive a standard therapeutic regimen including surgery and chemotherapy; simultaneously, drug resistance and adverse effects are reported in a several patients. Therefore, the safer and more efficient diagnostic and treatment method for ovarian cancer is imperative. Scientists have been trying to utilize aptamer technology for the early diagnosis and accurate treatment of ovarian cancer and some progress has been made in this field. This review discusses the screening of nucleic acid aptamers by targeting ovarian cancer cells and the application of aptamers in the diagnosis and treatment of ovarian cancer.

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Extracellular vesicles derived from ascitic fluid enhance growth and migration of ovarian cancer cells

Scientific Reports ◽

10.1038/s41598-021-88163-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Aparna Mitra ◽

Kyoko Yoshida-Court ◽

Travis N. Solley ◽

Megan Mikkelson ◽

Chi Lam Au Yeung ◽

...

Keyword(s):

Ovarian Cancer ◽

Extracellular Vesicles ◽

Ovarian Cancer Cells ◽

High Grade ◽

Serous Ovarian Carcinoma ◽

Advanced Stages ◽

And Migration ◽

Cancer Spheroids ◽

Omental Fat ◽

Low Expression

AbstractOvarian cancer is associated with a high mortality rate due to diagnosis at advanced stages. Dissemination often occurs intraperitoneally within the ascites fluid. The microenvironment can support dissemination through several mechanisms. One potential ascites factor which may mediate dissemination are EVs or extracellular vesicles that can carry information in the form of miRNAs, proteins, lipids, and act as mediators of cellular communication. We present our observations on EVs isolated from ascitic supernatants from patients diagnosed with high grade serous ovarian carcinoma in augmenting motility, growth, and migration towards omental fat. MicroRNA profiling of EVs from malignant ascitic supernatant demonstrates high expression of miR 200c-3p, miR18a-5p, miR1246, and miR1290 and low expression of miR 100- 5p as compared to EVs isolated from benign ascitic supernatant. The migration of ovarian cancer spheroids towards omental fat is enhanced in the presence of malignant ascitic EVs. Gene expression of these cells showed increased expression of ZBED2, ZBTB20, ABCC3, UHMK1, and low expression of Transgelin and MARCKS. We present evidence that ovarian ascitic EVs increase the growth of ovarian cancer spheroids through miRNAs.

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Hybrid-Type SELEX for the Selection of Artificial Nucleic Acid Aptamers Exhibiting Cell Internalization Activity

Pharmaceutics ◽

10.3390/pharmaceutics13060888 ◽

2021 ◽

Vol 13 (6) ◽

pp. 888

Author(s):

Hiro Uemachi ◽

Yuuya Kasahara ◽

Keisuke Tanaka ◽

Takumi Okuda ◽

Yoshihiro Yoneda ◽

...

Keyword(s):

Nucleic Acid ◽

Surface Protein ◽

Functional Screening ◽

Nucleic Acid Aptamers ◽

Hybrid Type ◽

Cell Internalization ◽

Promising Target ◽

A Cell ◽

Exponential Enrichment

Nucleic acid aptamers have attracted considerable attention as next-generation pharmaceutical agents and delivery vehicles for small molecule drugs and therapeutic oligonucleotides. Chemical modification is an effective approach for improving the functionality of aptamers. However, the process of selecting appropriately modified aptamers is laborious because of many possible modification patterns. Here, we describe a hybrid-type systematic evolution of ligands by exponential enrichment (SELEX) approach for the generation of the artificial nucleic acid aptamers effective against human TROP2, a cell surface protein identified by drug discovery as a promising target for cancer therapy. Capillary electrophoresis SELEX was used for the pre-screening of multiple modified nucleic acid libraries and enrichment of TROP2 binding aptamers in the first step, followed by functional screening using cell-SELEX in the second step for the generation of cell-internalizing aptamers. One representative aptamer, Tac-B1, had a nanomolar-level affinity to human TROP2 and exhibited elevated capacity for internalization by cells. Because of the growing interest in the application of aptamers for drug delivery, our hybrid selection approach has great potential for the generation of functional artificial nucleic acid aptamers with ideal modification patterns in vitro.

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Biotin-streptavidin-guided two-step pretargeting approach using PLGA for molecular ultrasound imaging and chemotherapy for ovarian cancer

PeerJ ◽

10.7717/peerj.11486 ◽

2021 ◽

Vol 9 ◽

pp. e11486

Author(s):

Hang Zhou ◽

Jing Fu ◽

Qihuan Fu ◽

Yujie Feng ◽

Ruixia Hong ◽

...

Keyword(s):

Ovarian Cancer ◽

Ultrasound Imaging ◽

High Performance ◽

Encapsulation Efficiency ◽

Plga Nanoparticles ◽

Cell Counting ◽

Ovarian Cancer Cells ◽

Skov3 Cells ◽

Targeting Ability ◽

Targeting Strategy

Background Ovarian cancer seriously threatens the lives and health of women, and early diagnosis and treatment are still challenging. Pre-targeting is a promising strategy to improve the treatment efficacy of ovarian cancer and the results of ultrasound imaging. Purpose To explore the effects of a pre-targeting strategy using streptavidin (SA) and paclitaxel (PTX)-loaded phase-shifting poly lactic-co-glycolic acid (PLGA) nanoparticles with perfluoro-n-pentane (PTX-PLGA-SA/PFPs) on the treatment and ultrasound imaging of ovarian cancer. Methods PTX-PLGA/PFPs were prepared with a single emulsion (O/W) solvent evaporation method and SA was attached using carbodiimide. The encapsulation efficiency of PTX and the release characteristics were assessed with high performance liquid chromatography. The phase-change characteristics of the PTX-PLGA-SA/PFPs were investigated. The anti-carcinoembryonic antigen (CEA) antibody (Ab) was covalently attached to PTX-PLGA/PFPs via carbodiimide to create PTX-PLGA-Ab/PFPs. The targeting efficiency of the nanoparticles and the viability of ovarian cancer SKOV3 cells were evaluated in each group using a microscope, flow cytometry, and cell counting kit 8 assays. Results THE PTX-PLGA-SA/PFPs were spheres with a size of 383.0 ± 75.59 nm. The encapsulation efficiency and loading capability of the nanoparticles for PTX were 71.56 ± 6.51% and 6.57 ± 0.61%, respectively. PTX was burst-released up to 70% in 2–3 d. When irradiated at 7.5 W for 3 min, the PTX-PLGA-SA/PFPs visibly enhanced the ultrasonography images (P < 0.05). At temperatures of 45°C and 60°C the nanoparticles phase-shifted into micro-bubbles and the sizes increased. The binding efficiencies of SA and Ab to the PTX-PLGA/PFPs were 97.16 ± 1.20% and 92.74 ± 5.75%, respectively. Pre-targeting resulted in a high binding efficacy and killing effect on SKOV3 cells (P < 0.05). Conclusions The two-step pre-targeting process can significantly enhance the targeting ability of PTX-loaded PLGA nanoparticles for ovarian cancer cells and substantially improve the therapeutic efficacy. This technique provides a new method for ultrasonic imaging and precise chemotherapy for ovarian cancer.

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Cisplatin Loaded Hyaluronic Acid Modified TiO2Nanoparticles for Neoadjuvant Chemotherapy of Ovarian Cancer

Journal of Nanomaterials ◽

10.1155/2015/390358 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Enling Liu ◽

Yuxiu Zhou ◽

Zheng Liu ◽

Jun Li ◽

Donghong Zhang ◽

...

Keyword(s):

Ovarian Cancer ◽

Hyaluronic Acid ◽

Neoadjuvant Chemotherapy ◽

Tumor Targeting ◽

Ovarian Cancer Cells ◽

Release Property ◽

Decreasing Ph ◽

Targeting Ability

Novel tumor-targeting titanium dioxide (TiO2) nanoparticles modified with hyaluronic acid (HA) were developed to explore the feasibility of exploiting the pH-responsive drug release property ofTiO2and the tumor-targeting ability of HA to construct a tumor-targeting cisplatin (CDDP) delivery system (HA-TiO2) for potential neoadjuvant chemotherapy of ovarian cancer. The experimental results indicated that CDDP release from the HA-TiO2nanoparticles was significantly accelerated by decreasing pH from 7.4 to 5.0, which is of particular benefit to cancer therapy. CDDP-loaded HA-TiO2nanoparticles increased the accumulation of CDDP in A2780 ovarian cancer cells via HA-mediated endocytosis and exhibited superior anticancer activityin vitro.In vivoreal-time imaging assay revealed that HA-TiO2nanoparticles possessed preferable tumor-targeting ability which might potentially minimize the toxic side effects of CDDP in clinical application.

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Mechanisms of Apoptosis-Related Long Non-coding RNAs in Ovarian Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.641963 ◽

2021 ◽

Vol 9 ◽

Author(s):

Toshihiko Takeiwa ◽

Kazuhiro Ikeda ◽

Kuniko Horie-Inoue ◽

Satoshi Inoue

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Therapy Resistance ◽

Therapeutic Strategies ◽

Regulatory Mechanisms ◽

Ovarian Cancer Cells ◽

Regulation Of Transcription ◽

Advanced Stages ◽

Non Coding Rnas

Ovarian cancer is a health-threatening malignancy of ovary in female reproductive systems and one of the most common gynecological malignancies worldwide. Due to rare early symptoms, ovarian cancers are often diagnosed at advanced stages and exhibit poor prognosis. Thus, efforts have been paid to develop alternative diagnostic and therapeutic strategies for the disease. Recent studies have presented that some long non-coding RNAs (lncRNAs) play roles in apoptosis of ovarian cancer cells through various mechanisms involved in the regulation of transcription factors, histone modification complexes, miRNAs, and protein stability. Because evasion of apoptosis in cancer cells facilitates to promote tumor progression and therapy resistance, apoptosis regulatory mechanisms of lncRNAs may be promising new targets in ovarian cancer. In this review, we introduce the recent findings in regard to the molecular mechanisms of apoptosis-related lncRNAs in ovarian cancer cells.

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Abstract B42: Identification of nucleic acid aptamers for ovarian cancer biomarkers using multiple selection modes and high-throughput sequencing.

10.1158/1557-3265.ovca15-b42 ◽

2016 ◽

Author(s):

Rebecca J. Whelan ◽

Arvinder Kapur ◽

Mildred Felder ◽

Jamie Shallcross ◽

Manish S. Patankar

Keyword(s):

Ovarian Cancer ◽

Nucleic Acid ◽

High Throughput ◽

High Throughput Sequencing ◽

Cancer Biomarkers ◽

Nucleic Acid Aptamers

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The evolving role of MUC16 (CA125) in the transformation of ovarian cells and the progression of neoplasia

Carcinogenesis ◽

10.1093/carcin/bgab010 ◽

2021 ◽

Author(s):

Panagiotis Giamougiannis ◽

Pierre L Martin-Hirsch ◽

Francis L Martin

Keyword(s):

Ovarian Cancer ◽

Ovarian Cancer Cells ◽

Cancer Antigen ◽

Transmembrane Glycoprotein ◽

Ovarian Cells ◽

Advanced Stages ◽

Metastatic Process ◽

Membrane Bound ◽

Insight Into

Abstract MUC16 (the cancer antigen CA125) is the most commonly used serum biomarker in epithelial ovarian cancer, with increasing levels reflecting disease progression. It is a transmembrane glycoprotein with multiple isoforms, undergoing significant changes through the metastatic process. Aberrant glycosylation and cleavage with overexpression of a small membrane-bound fragment consist MUC16-related mechanisms that enhance malignant potential. Even MUC16 knockdown can induce an aggressive phenotype but can also increase susceptibility to chemotherapy. Variable MUC16 functions help ovarian cancer cells avoid immune cytotoxicity, survive inside ascites and form metastases. This review provides a comprehensive insight into MUC16 transformations and interactions, with description of activated oncogenic signalling pathways, and adds new elements on the role of its differential glycosylation. By following the journey of the molecule from pre-malignant states to advanced stages of disease it demonstrates its behaviour, in relation to the phenotypic shifts and progression of ovarian cancer. Additionally it presents proposed differences of MUC16 structure in normal/benign conditions and epithelial ovarian malignancy.

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