Aptamers as potential therapeutic agents for ovarian cancer

Henri, Justin; Macdonald, Joanna; Strom, Mia; Duan, Wei; Shigdar, Sarah

doi:10.1016/j.biochi.2017.12.001

Cited by 18 publications

(9 citation statements)

References 134 publications

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“…This reduces the hydrophobic contact between the aromatic ring of DOX and the DNA bases, leading to drug release [33]. Through being internalized by an endocytic pathway, aptamer-DOX conjugates are exposed to the required pH in the lysosome, resulting in drug release into the cytoplasm, allowing DOX to avoid Pgp pumps present on the cell membrane [45].…”

Section: Discussionmentioning

confidence: 99%

Bifunctional Aptamer–Doxorubicin Conjugate Crosses the Blood–Brain Barrier and Selectively Delivers Its Payload to EpCAM-Positive Tumor Cells

Macdonald

Denoyer

Henri

et al. 2020

Nucleic Acid Therapeutics

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The prognosis for breast cancer patients diagnosed with brain metastases is poor, with survival time measured merely in months. This can largely be attributed to the limited treatment options capable of reaching the tumor as a result of the highly restrictive blood-brain barrier (BBB). While methods of overcoming this barrier have been developed and employed with current treatment options, the majority are highly invasive and nonspecific, leading to severe neurotoxic side effects. A novel approach to address these issues is the development of therapeutics targeting receptor-mediated transport mechanisms on the BBB endothelial cell membranes. Using this approach, we intercalated doxorubicin (DOX) into a bifunctional aptamer targeting the transferrin receptor on the BBB and epithelial cell adhesion molecule (EpCAM) on metastatic cancer cells. The ability of the DOXloaded aptamer to transcytose the BBB and selectively deliver the payload to EpCAM-positive tumors was evaluated in an in vitro model and confirmed for the first time in vivo using the MDA-MB-231 breast cancer metastasis model (MDA-MB-231Br). We show that colocalized aptamer and DOX are clearly detectable within the brain lesions 75 min postadministration. Collectively, results from this study demonstrate that through intercalation of a cytotoxic drug into the bifunctional aptamer, a therapeutic delivery vehicle can be developed for specific targeting of EpCAM-positive brain metastases.

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Section: Discussionmentioning

confidence: 99%

Bifunctional Aptamer–Doxorubicin Conjugate Crosses the Blood–Brain Barrier and Selectively Delivers Its Payload to EpCAM-Positive Tumor Cells

Macdonald

Denoyer

Henri

et al. 2020

Nucleic Acid Therapeutics

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“…Ovarian cancer is the most fatal gynecological malignancy, leading to more deaths than that of all other gynecological cancers combined, thereby being a significant threat to women’s health. Worldwide, approximately 240,000 new cases are reported annually, about two-thirds of which are fatal ( Henri et al, 2018 ). Symptoms of ovarian cancer, such as abdominal distension, indigestion, and nausea, are nonspecific; therefore, ovarian cancer is often misdiagnosed as gastrointestinal ailments and is difficult to diagnose at an early stage ( Liu et al, 2019 ), with approximately 75% patients diagnosed at advanced FIGO stages ( Hoosen et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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

Ruan

2021

Front. Genet.

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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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“…Owing to their low immunogenicity, high target specificity, high stability, and high sensitivity, aptamers have attracted a lot of attention in the area of molecular biology and are likely to become the new molecular probes . Therefore, identification of novel aptamers has broad applications and is important for disease prognosis (eg, metastasis prediction), target drug identification, and evaluation of therapeutic effects …”

Section: Introductionmentioning

confidence: 99%

“…21 Owing to their low immunogenicity, high target specificity, high stability, and high sensitivity, aptamers have attracted a lot of attention in the area of molecular biology and are likely to become the new molecular probes. [22][23][24][25][26][27][28][29][30][31][32][33][34] Therefore, identification of novel aptamers has broad applications and is important for disease prognosis (eg, metastasis prediction), target drug identification, 35 and evaluation of therapeutic effects. 36 In this study, we used aH pylori surface recombinant antigen (HP-Ag) as a target to select unique nucleic acid aptamers that can be used for detection of H pylori infection.…”

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confidence: 99%

Recognition of Helicobacter pylori by protein‐targeting aptamers

Yan

Ren

et al. 2019

Helicobacter

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Background Helicobacter pylori (H pylori) is a disease‐causing pathogen capable of surviving under acidic conditions of the human stomach. Almost half of the world's population is infected with H pylori, with gastric cancer being the most unsatisfactory prognosis. Although H pylori has been discovered 30 years ago, the effective treatment and elimination of H pylori continue to be problematic. Materials and methods In our study, we screened nucleic acid aptamers using H pylori surface recombinant antigens as targets. Trypsin was used for separating aptamers that were bound to proteins. Following nine rounds of screening, we performed sequence similarity analyses to assess whether the aptamers can recognize the target protein. Two sequences with desirable recognition ability were selected for affinity detection. Aptamer Hp4 with the strongest binding ability to the H pylori surface recombinant antigen was chosen. After optimization of the binding conditions, we conducted specificity tests for Hp4 using Escherichia coli, Staphylococcus aureus, Vibrioanguillarum, and H pylori. Results The data indicated that the aptamer Hp4 had an equilibrium dissociation constant (Kd) of 26.48 ± 5.72 nmol/L to the target protein. This aptamer was capable of exclusively detecting H pylori cells, without displaying any specificity for other bacteria. Conclusions We obtained a high‐affinity aptamer for H pylori, which is expected to serve as a new molecular probe for detection of H pylori.

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Aptamers as potential therapeutic agents for ovarian cancer

Cited by 18 publications

References 134 publications

Bifunctional Aptamer–Doxorubicin Conjugate Crosses the Blood–Brain Barrier and Selectively Delivers Its Payload to EpCAM-Positive Tumor Cells

Bifunctional Aptamer–Doxorubicin Conjugate Crosses the Blood–Brain Barrier and Selectively Delivers Its Payload to EpCAM-Positive Tumor Cells

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

Recognition of Helicobacter pylori by protein‐targeting aptamers

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