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Histological types of lung cancer tissues used in the selection of aptamers against epithelial cell adhesion molecule (EpCAM).
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We selected DNA aptamers to the epithelial cell adhesion molecule (EpCAM) expressed on primary lung cancer cells isolated from the tumors of patients with non-small cell lung cancer using competitive displacement of aptamers from EpCAM by a corresponding antibody. The resulting aptamers clones showed good nanomolar affinity to EpCAM-positive lung c...
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Background:
Improving anti-cancer drug delivery performance can be achieved through designing smart and targeted drug delivery systems (DDSs). For this aim, it is important to evaluate overexpressed biomarkers in the tumor microenvironment (TME) for optimizing DDSs.
Materials and methods:
Herein, we designed a novel DDS based on magnetic mesopor...
The development and performance of a DNA probe adsorbing Mn²⁺-modified black phosphorus (BP@Mn²⁺/DNA) hybrid nanosensor is reported that enables rapid detection of cancer-derived exosomal microRNAs (miRNAs) and exosomes. This two-dimensional (2D) nanosensor can spontaneously penetrate the lipid bilayer of exosome membranes owing to its ultra-thin g...
A simple and wash-free POCT platform based on microcapillary was developed, using breast cancer cell-derived exosomes as a model. This method adopted the “one suction and one extrusion” mode. The hybridized complex of epithelial cell adhesion molecule (EpCAM) aptamer and complementary DNA-horseradish peroxidase conjugate (CDNA-HRP) was pre-modified...
To overcome the lack of selectivity and nonspecific biodistribution of drugs in the body, targeted delivery of chemotherapeutic agents with aptamers is a very effective method. In this strategy, aptamers could be specifically identified and attach to targeted molecules on the cancerous cells and deliver the chemotherapeutic agents to desired tissue...
Purpose
The clinical management of patients with castration-resistant prostate cancer (CRPC) is difficult. However, novel treatment methods are gradually being introduced. Considering the adverse effects of traditional treatments, recent studies have investigated gene therapy as a method to combat CRPC; but, the application of long non-coding (lnc)...
Citations
... To test the hypothesis, CTCs and circulating tumor microemboli (CTMs) were isolated from the patient's blood using the protocol described previously (Zamay et al., 2019). CTCs and CTMs were captured with the biotinylated aptamer MDA231 attached to streptavidin-coated magnetic beads and stained with the same Cy3labeled aptamer. ...
Introduction: Breast cancer (BC) diagnostics lack noninvasive methods and procedures for screening and monitoring disease dynamics. Admitted CellSearch® is used for fluid biopsy and capture of circulating tumor cells of only epithelial origin. Here we describe an RNA aptamer (MDA231) for detecting BC cells in clinical samples, including blood. The MDA231 aptamer was originally selected against triple-negative breast cancer cell line MDA-MB-231 using cell-SELEX.
Methods: The aptamer structure in solution was predicted using mFold program and molecular dynamic simulations. The affinity and specificity of the evolved aptamers were evaluated by flow cytometry and laser scanning microscopy on clinical tissues from breast cancer patients. CTCs were isolated form the patients’ blood using the developed method of aptamer-based magnetic separation. Breast cancer origin of CTCs was confirmed by cytological, RT-qPCR and Immunocytochemical analyses.
Results: MDA231 can specifically recognize breast cancer cells in surgically resected tissues from patients with different molecular subtypes: triple-negative, Luminal A, and Luminal B, but not in benign tumors, lung cancer, glial tumor and healthy epithelial from lungs and breast. This RNA aptamer can identify cancer cells in complex cellular environments, including tumor biopsies (e.g., tumor tissues vs. margins) and clinical blood samples (e.g., circulating tumor cells). Breast cancer origin of the aptamer-based magnetically separated CTCs has been proved by immunocytochemistry and mammaglobin mRNA expression.
Discussion: We suggest a simple, minimally-invasive breast cancer diagnostic method based on non-epithelial MDA231 aptamer-specific magnetic isolation of circulating tumor cells. Isolated cells are intact and can be utilized for molecular diagnostics purposes.
... Alternative receptors for capturing CTCs are aptamers against the same surface proteins used for immunocapturing. Several aptamers, both RNA (Shigdar et al., 2011) and DNA (Alshaer et al., 2017;Song et al., 2013;Zamay et al., 2019), targeting EpCAM have been selected. The first one was an RNA obtained using as target a recombinant form of the C-terminal cytoplasmic domain of EpCAM (Shigdar et al., 2011). ...
... An alternative approach is to obtain aptamers recognizing the native form of the protein on the tumor cells. This was achieved with lung cancer cells, using as target during the SELEX process cells isolated from tumors of patients (Zamay et al., 2019). But, to our knowledge, there are no aptamers evolved against the native form of EpCAM on PCa cells. ...
In men, prostate cancer is the most frequently diagnosed malignancy worldwide. Early diagnosis improves its prognosis, with higher survival rates and a better quality of life for patients. However, diagnosis and characterization of tumors are mainly based on highly invasive tissue biopsies, with an incomplete representation of the entire tumor. In consequence, attention is turning to the so-called liquid biopsies, which provide molecular information about the tumor by detecting its specific components, including proteins, circulating nucleic acids or tumor cells, in bodily fluids such as blood or urine. Recent years have seen the development of a large number of electrochemical sensors employing oligonucleotides for the recognition of prostate tumor components in a minimal invasive way. Here we survey the reported designs, which are categorized as aptasensors and genosensors for the different molecular components identified as prostate cancer biomarkers. We present a critical evaluation of their analytical validity, identifying the challenges of bringing these devices to the clinical practice.
... CTCs (Zamay et al., 2019). For example, Lee Group has developed a new microfluidic platform that integrates fieldeffect transistors (FETs) and chambers for automatic detection and counting of CTCs ( Figure 2C). ...
Tumor metastasis is one of the main causes of cancer incidence and death worldwide. In the process of tumor metastasis, the isolation and analysis of circulating tumor cells (CTCs) plays a crucial role in the early diagnosis and prognosis of cancer patients. Due to the rarity and inherent heterogeneity of CTCs, there is an urgent need for reliable CTCs separation and detection methods in order to obtain valuable information on tumor metastasis and progression from CTCs. Microfluidic technology is increasingly used in various studies of CTCs separation, identification and characterization because of its unique advantages, such as low cost, simple operation, less reagent consumption, miniaturization of the system, rapid detection and accurate control. This paper reviews the research progress of microfluidic technology in CTCs separation and detection in recent years, as well as the potential clinical application of CTCs, looks forward to the application prospect of microfluidic technology in the treatment of tumor metastasis, and briefly discusses the development prospect of microfluidic biosensor.
... In addition to differential approaches, whole-living cell-based protocols have been applied by the same group for the selection of aptamers against NSCLC-related known targets [20]. The authors addressed the selection of DNA aptamers against the epithelial cell adhesion molecule (EpCAM), a marker expressed at high levels by many carcinomas as well as by circulating tumor cells [21,22]. ...
... Differential-cell SELEX ssDNAs HLAMP cells A549 cells [14] Differential-cell SELEX ssDNAs Human blood cells CD90 + A549 cells [15] Differential-cell SELEX 2 F-Py-RNAs H460 cells A549 cells [17] Differential-cell SELEX ssDNAs Cells from healthy lung tissues and blood cells from healthy person Lung cells derived from postoperative adenocarcinoma tissues [19] Competitive-cell SELEX ssDNAs -Primary lung cancer cells overexpressing EpCAM [20] In vivo SELEX 2 F-Py-PEG-RNAs -NCI-H460 tumor xenograft mice [23] 3. Nucleic Acid Aptamers for NSCLC Detection ...
... The possibility to use aptamers for the detection of CTCs was also described by Zamay et al. [19,20]. They found that fluorescently labeled aptamers selected against lung adenocarcinoma cells from postoperative tissues, when applied to patients' peripheral blood samples, were able to detect CTCs, with a specificity of 76% and a sensitivity of 86% [19]. ...
Messenger RNAs (mRNAs) present a great potential as therapeutics for the treatment and prevention of a wide range of human pathologies, allowing for protein replacement, vaccination, cancer immunotherapy, and genomic engineering. Despite advances in the design of mRNA-based therapeutics, a key aspect for their widespread translation to clinic is the development of safe and effective delivery strategies. To this end, non-viral delivery systems including peptide-based complexes, lipidic or polymeric nanoparticles, and hybrid formulations are attracting growing interest. Despite displaying somewhat reduced efficacy compared to viral-based systems, non-viral carriers offer important advantages in terms of biosafety and versatility. In this review, we provide an overview of current mRNA therapeutic applications and discuss key biological barriers to delivery and recent advances in the development of non-viral systems. Challenges and future applications of this novel therapeutic modality are also discussed.
... The strategy showed high specificity for discriminating normal cells and leukocytes, and the detection limit was 10 cells/mL. Zamay et al. used a targeted selection of DNA aptamers and applied two different aptamer clones for the isolation and detection of CTCs in peripheral blood samples from patients with different lung cancer types and benign lung tumors [130]. In addition, these aptamers were further utilized for a bioluminescent solid-phase sandwich-type microassay to detect lung tumor elements circulating in the blood [131]. ...
The early detection of cancer favors a greater chance of curative treatment and long-term survival. Exciting new technologies have been developed that can help to catch the disease early. Liquid biopsy is a promising non-invasive tool to detect cancer, even at an early stage, as well as to continuously monitor disease progression and treatment efficacy. Various methods have been implemented to isolate and purify bio-analytes in liquid biopsy specimens. Aptamers are short oligonucleotides consisting of either DNA or RNA that are capable of binding to target molecules with high specificity. Due to their unique properties, they are considered promising recognition ligands for the early detection of cancer by liquid biopsy. A variety of circulating targets have been isolated with high affinity and specificity by facile modification and affinity regulation of the aptamers. In this review, we discuss recent progress in aptamer-mediated liquid biopsy for cancer detection, its associated challenges, and its future potential for clinical applications.
... Moreover, the burgeoning SELEX technology makes it possible to select personalized aptamers for each patient. It has been reported that primary cancerous cells and biopsies directly originating from patients have been used for individual tumor-specific aptamer selection Takakura et al., 2019;Zamay et al., 2019). Additionally, organoid technology has become one of the most important breakthroughs, so patientderived tumoroid-based SELEX is likely to exhibit exciting potential prospects for personalized ApDC treatment. ...
Paclitaxel (PTX) has been used for cancer treatment for decades and has become one of the most successful chemotherapeutics in the clinic and financially. However, serious problems with its use still exist, owing to its poor solubility and non-selective toxicity. With respect to these issues, recent advances have addressed the water solubility and tumor specificity related to PTX application. Many measures have been proposed to remedy these limitations by enhancing tumor recognition via ligand-receptor-mediated targeting as well as other associated strategies. In this review, we investigated various kinds of ligands that have emerged as PTX tumor-targeting tools. In particular, this article highlights small molecule-, protein-, and aptamer-functionalized conjugates and nanoparticles (NPs), providing a promising approach for PTX-based individualized treatment prospects.
... Another thematic focus in this Special Issue addresses cells as biomarkers discussing tumor-associated circulating endothelial cells (tCECs) as a new diagnostic marker for prostate cancer [9], the detailed quantification of leukocytes in peripheral blood to distinguish head and neck squamous cell carcinoma cancer patients from healthy individuals [10], the utility of peripheral blood mononuclear cells (PBMCs) as a marker to assess the response of NSCLC patients to nivolumab therapy [11] and the development of a highly efficient technique that allows the detection of circulating tumor cells in blood samples from NSCLC patients [12]. Moreover, Payne et al. review the status quo of diagnosing head and neck cancer with the help of circulating tumor cells and cast a glance at potential new applications of this method [13]. ...
In this Special Issue of Cancers, the latest insights on biomarkers in cancers are presented in 33 up-to-the-minute research papers and reviews summing up the tremendous progress in this interesting and important field of research. The recent development of new therapeutic approaches has provided clinicians with more efficient tools than ever before for the treatment of cancerous diseases. However, choosing the right option requires to [...]
... With the surge of attention inclined toward EpCAM markers, Zamay et al. screened and designed two aptamers (ECM-APT-01 and ECM-APT-2) from the tissues of primary lung cancer patients with a ligand-guided selection approach and sequenced using next-generation sequencing technology. 95 Furthermore, these aptamer clones can be subjected to targeting of CTCs in patients by conjugating them to a potential nanocarrier. Likewise, much earlier in 2013, Song et al. successfully optimized the SYL3C aptamer against EpCAM, which captured CTCs with 63% efficiency and 80% purity. ...
The incessant transitions occurring in a cancer cell in response to cancer therapy have put forth a lot of irreversible consequences, eventuating a high mortality rate. This upsurge in morbidity and fatality is rationalized by the unilateral modes of conventional treatment regimens such as chemotherapy and radiation therapy. Eventually, the advent of nanotechnology in cancer medicine has unfolded a plethora of efficient ways to tackle the impediments associated with current treatment modalities such as metastasis, relapse, and therapy resistance. Active targeting guides nanocarriers for not just mitigating the drug payload but also minimizing the off-target side effects. Nanotherapeutics emphasizes this multidimensional approach and has portrayed promising preclinical outcomes, but clinical assessments need yet to be validated. This review discusses and elaborates on the oligonucleotide aptamer–nanoparticles leveraging active targeting and its applications in multifarious therapeutic interventions for the eradication of cancer. This, in combination with the various technological gains in aptamer synthesis, projects its potential contribution in the facet of nanomedicine.
... In addition to differential approaches, whole-living cell-based protocols have been applied by the same group for the selection of aptamers against NSCLC-related known targets [20]. The authors addressed the selection of DNA aptamers against the epithelial cell adhesion molecule (EpCAM), a marker expressed at high levels by many carcinomas as well as by circulating tumor cells [21,22]. ...
... Differential-cell SELEX ssDNAs HLAMP cells A549 cells [14] Differential-cell SELEX ssDNAs Human blood cells CD90 + A549 cells [15] Differential-cell SELEX 2 F-Py-RNAs H460 cells A549 cells [17] Differential-cell SELEX ssDNAs Cells from healthy lung tissues and blood cells from healthy person Lung cells derived from postoperative adenocarcinoma tissues [19] Competitive-cell SELEX ssDNAs -Primary lung cancer cells overexpressing EpCAM [20] In vivo SELEX 2 F-Py-PEG-RNAs -NCI-H460 tumor xenograft mice [23] 3. Nucleic Acid Aptamers for NSCLC Detection ...
... The possibility to use aptamers for the detection of CTCs was also described by Zamay et al. [19,20]. They found that fluorescently labeled aptamers selected against lung adenocarcinoma cells from postoperative tissues, when applied to patients' peripheral blood samples, were able to detect CTCs, with a specificity of 76% and a sensitivity of 86% [19]. ...
Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer worldwide, with the highest incidence in developed countries. NSCLC patients often face resistance to currently available therapies, accounting for frequent relapses and poor prognosis. Indeed, despite great recent advancements in the field of NSCLC diagnosis and multimodal therapy, most patients are diagnosed at advanced metastatic stage, with a very low overall survival. Thus, the identification of new effective diagnostic and therapeutic options for NSCLC patients is a crucial challenge in oncology. A promising class of targeting molecules is represented by nucleic-acid aptamers, short single-stranded oligonucleotides that upon folding in particular three dimensional (3D) structures, serve as high affinity ligands towards disease-associated proteins. They are produced in vitro by SELEX (systematic evolution of ligands by exponential enrichment), a combinatorial chemistry procedure, representing an important tool for novel targetable biomarker discovery of both diagnostic and therapeutic interest. Aptamer-based approaches are promising options for NSCLC early diagnosis and targeted therapy and may overcome the key obstacles of currently used therapeutic modalities, such as the high toxicity and patients’ resistance. In this review, we highlight the most important applications of SELEX technology and aptamers for NSCLC handling.
... In contrast to the usual procedure of obtaining an EpCAM-specific aptamer by application of a selection process, such as cell-SELEX (e.g. [50]), Bell et al. [51] investigated selection in silico, which they say is highly sought after to facilitate virtual screening and increased understanding of important nucleic acidprotein interactions. In silico selection can also be a valuable adjunct for facilitating selection of a desired aptamer in the lab or optimization of sequence, and adding post-selection modifications to increase binding to target. ...
Aptamers are typically defined as relatively short (20 to 60 nucleotides) single-stranded DNA or RNA molecules that bind with high affinity and specificity to various types of targets. Aptamers are frequently referred to as “synthetic antibodies” but are easier to obtain, less expensive to produce, and in several ways more versatile than antibodies. The beginnings of aptamers date back to 1990, and since then there has been a continual increase in aptamer publications. The intent of the present account was to focus on recent original research publications, i.e., those appearing in 2019 through April 2020, when this account was written. A Google Scholar search of this recent literature was performed for relevance-ranking of articles. New methods for selection of aptamers were not included. Nine categories of applications were organized and representative examples of each are given. Finally, an outlook is offered focusing on “faster, better, cheaper” application performance factors as key drivers for future innovations in aptamer applications.
