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Pharmaceuticals
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Aptamer-Based Diagnostics and Therapeutics
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Aptamer-Based Diagnostics and Therapeutics

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (31 October 2018) | Viewed by 75061

Special Issue Editor

Dr. Sarah Shigdar

E-Mail Website
Guest Editor
1. School of Medicine, Deakin University, Geelong, VIC 3128, Australia
2. Centre for Molecular and Medical Research, Deakin University, Geelong, VIC 3128, Australia
Interests: aptamers; drug development; novel therapeutics in cancer treatment; targeted drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We invite authors to submit papers to Pharmaceuticals on the exciting field of aptamer diagnostics and therapeutics. This Special Issue aims to include original papers and review articles on basic or clinical research on aptamers, including aptamer conjugates, aptamer nanoparticles, spiegelmers, peptide aptamers, locked aptamers and different aptamer applications, including applications in diagnostics, imaging, therapy, sensors or other technology development, aptamer pharmacology, biomarker discovery or clinical applications.

Dr. Sarah Shigdar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • aptamers
  • aptamer conjugates
  • aptamer diagnostics
  • aptamer nanoparticles
  • aptamer imaging
  • aptamer sensors
  • aptamer therapy
  • aptamer theranostics

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Published Papers (12 papers)

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Editorial

Jump to: Review

3 pages, 150 KiB  
Editorial
Aptamer-Based Diagnostics and Therapeutics
by Sarah Shigdar
Pharmaceuticals 2019, 12(1), 6; https://doi.org/10.3390/ph12010006 - 02 Jan 2019
Cited by 7 | Viewed by 2719
Abstract
Aptamers were first described almost 30 years ago, with the publication of three separate research papers describing how a randomized library of RNA sequences could be incubated with a target to find a sequence that specifically binds via van der Waals forces, covalent [...] Read more.
Aptamers were first described almost 30 years ago, with the publication of three separate research papers describing how a randomized library of RNA sequences could be incubated with a target to find a sequence that specifically binds via van der Waals forces, covalent and hydrogen bonding, and not Watson Crick base pairing [...] Full article
(This article belongs to the Special Issue Aptamer-Based Diagnostics and Therapeutics)

Review

Jump to: Editorial

20 pages, 557 KiB  
Review
Radiolabelled Aptamers for Theranostic Treatment of Cancer
by Umair Khalid, Chris Vi, Justin Henri, Joanna Macdonald, Peter Eu, Giovanni Mandarano and Sarah Shigdar
Pharmaceuticals 2019, 12(1), 2; https://doi.org/10.3390/ph12010002 - 24 Dec 2018
Cited by 15 | Viewed by 5583
Abstract
Cancer has a high incidence and mortality rate worldwide, which continues to grow as millions of people are diagnosed annually. Metastatic disease caused by cancer is largely responsible for the mortality rates, thus early detection of metastatic tumours can improve prognosis. However, a [...] Read more.
Cancer has a high incidence and mortality rate worldwide, which continues to grow as millions of people are diagnosed annually. Metastatic disease caused by cancer is largely responsible for the mortality rates, thus early detection of metastatic tumours can improve prognosis. However, a large number of patients will also present with micrometastasis tumours which are often missed, as conventional medical imaging modalities are unable to detect micrometastases due to the lack of specificity and sensitivity. Recent advances in radiochemistry and the development of nucleic acid based targeting molecules, have led to the development of novel agents for use in cancer diagnostics. Monoclonal antibodies may also be used, however, they have inherent issues, such as toxicity, cost, unspecified binding and their clinical use can be controversial. Aptamers are a class of single-stranded RNA or DNA ligands with high specificity, binding affinity and selectivity for a target, which makes them promising for molecular biomarker imaging. Aptamers are presented as being a superior choice over antibodies because of high binding affinity and pH stability, amongst other factors. A number of aptamers directed to cancer cell markers (breast, lung, colon, glioblastoma, melanoma) have been radiolabelled and characterised to date. Further work is ongoing to develop these for clinical applications. Full article
(This article belongs to the Special Issue Aptamer-Based Diagnostics and Therapeutics)
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21 pages, 1536 KiB  
Review
TNBC Challenge: Oligonucleotide Aptamers for New Imaging and Therapy Modalities
by Simona Camorani, Monica Fedele, Antonella Zannetti and Laura Cerchia
Pharmaceuticals 2018, 11(4), 123; https://doi.org/10.3390/ph11040123 - 13 Nov 2018
Cited by 35 | Viewed by 6798
Abstract
Compared to other breast cancers, triple-negative breast cancer (TNBC) usually affects younger patients, is larger in size, of higher grade and is biologically more aggressive. To date, conventional cytotoxic chemotherapy remains the only available treatment for TNBC because it lacks expression of the [...] Read more.
Compared to other breast cancers, triple-negative breast cancer (TNBC) usually affects younger patients, is larger in size, of higher grade and is biologically more aggressive. To date, conventional cytotoxic chemotherapy remains the only available treatment for TNBC because it lacks expression of the estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2), and no alternative targetable molecules have been identified so far. The high biological and clinical heterogeneity adds a further challenge to TNBC management and requires the identification of new biomarkers to improve detection by imaging, thus allowing the specific treatment of each individual TNBC subtype. The Systematic Evolution of Ligands by EXponential enrichment (SELEX) technique holds great promise to the search for novel targetable biomarkers, and aptamer-based molecular approaches have the potential to overcome obstacles of current imaging and therapy modalities. In this review, we highlight recent advances in oligonucleotide aptamers used as imaging and/or therapeutic agents in TNBC, discussing the potential options to discover, image and hit new actionable targets in TNBC. Full article
(This article belongs to the Special Issue Aptamer-Based Diagnostics and Therapeutics)
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21 pages, 1837 KiB  
Review
Aptamer-iRNAs as Therapeutics for Cancer Treatment
by Mario M. Soldevilla, Daniel Meraviglia-Crivelli de Caso, Ashwathi P. Menon and Fernando Pastor
Pharmaceuticals 2018, 11(4), 108; https://doi.org/10.3390/ph11040108 - 18 Oct 2018
Cited by 38 | Viewed by 5872
Abstract
Aptamers are single-stranded oligonucleotides (ssDNA or ssRNA) that bind and recognize their targets with high affinity and specificity due to their complex tertiary structure. Aptamers are selected by a method called SELEX (Systematic Evolution of Ligands by EXponential enrichment). This method has allowed [...] Read more.
Aptamers are single-stranded oligonucleotides (ssDNA or ssRNA) that bind and recognize their targets with high affinity and specificity due to their complex tertiary structure. Aptamers are selected by a method called SELEX (Systematic Evolution of Ligands by EXponential enrichment). This method has allowed the selection of aptamers to different types of molecules. Since then, many aptamers have been described for the potential treatment of several diseases including cancer. It has been described over the last few years that aptamers represent a very useful tool as therapeutics, especially for cancer therapy. Aptamers, thanks to their intrinsic oligonucleotide nature, present inherent advantages over other molecules, such as cell-based products. Owing to their higher tissue penetrability, safer profile, and targeting capacity, aptamers are likely to become a novel platform for the delivery of many different types of therapeutic cargos. Here we focus the review on interfering RNAs (iRNAs) as aptamer-based targeting delivered agents. We have gathered the most reliable information on aptamers as targeting and carrier agents for the specific delivery of siRNAs, shRNA, microRNAs, and antisense oligonucleotides (ASOs) published in the last few years in the context of cancer therapy. Full article
(This article belongs to the Special Issue Aptamer-Based Diagnostics and Therapeutics)
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20 pages, 5934 KiB  
Review
Radiolabeling of Nucleic Acid Aptamers for Highly Sensitive Disease-Specific Molecular Imaging
by Leila Hassanzadeh, Suxiang Chen and Rakesh N. Veedu
Pharmaceuticals 2018, 11(4), 106; https://doi.org/10.3390/ph11040106 - 15 Oct 2018
Cited by 23 | Viewed by 6474
Abstract
Aptamers are short single-stranded DNA or RNA oligonucleotide ligand molecules with a unique three-dimensional shape, capable of binding to a defined molecular target with high affinity and specificity. Since their discovery, aptamers have been developed for various applications, including molecular imaging, particularly nuclear [...] Read more.
Aptamers are short single-stranded DNA or RNA oligonucleotide ligand molecules with a unique three-dimensional shape, capable of binding to a defined molecular target with high affinity and specificity. Since their discovery, aptamers have been developed for various applications, including molecular imaging, particularly nuclear imaging that holds the highest potential for the clinical translation of aptamer-based molecular imaging probes. Their easy laboratory production without any batch-to-batch variations, their high stability, their small size with no immunogenicity and toxicity, and their flexibility to incorporate various functionalities without compromising the target binding affinity and specificity make aptamers an attractive class of targeted-imaging agents. Aptamer technology has been utilized in nuclear medicine imaging techniques, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET), as highly sensitive and accurate biomedical imaging modalities towards clinical diagnostic applications. However, for aptamer-targeted PET and SPECT imaging, conjugation of appropriate radionuclides to aptamers is crucial. This review summarizes various strategies to link the radionuclides to chemically modified aptamers to accomplish aptamer-targeted PET and SPECT imaging. Full article
(This article belongs to the Special Issue Aptamer-Based Diagnostics and Therapeutics)
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24 pages, 321 KiB  
Review
Molecular Application of Aptamers in the Diagnosis and Treatment of Cancer and Communicable Diseases
by Philisiwe Fortunate Molefe, Priscilla Masamba, Babatunji Emmanuel Oyinloye, Londiwe Simphiwe Mbatha, Mervin Meyer and Abidemi Paul Kappo
Pharmaceuticals 2018, 11(4), 93; https://doi.org/10.3390/ph11040093 - 28 Sep 2018
Cited by 15 | Viewed by 5174
Abstract
Cancer and infectious diseases such as Ebola, HIV, tuberculosis, Zika, hepatitis, measles and human schistosomiasis are serious global health hazards. The increasing annual morbidities and mortalities of these diseases have been blamed on drug resistance and the inefficacy of available diagnostic tools, particularly [...] Read more.
Cancer and infectious diseases such as Ebola, HIV, tuberculosis, Zika, hepatitis, measles and human schistosomiasis are serious global health hazards. The increasing annual morbidities and mortalities of these diseases have been blamed on drug resistance and the inefficacy of available diagnostic tools, particularly those which are immunologically-based. Antibody-based tools rely solely on antibody production for diagnosis and for this reason they are the major cause of diagnostic delays. Unfortunately, the control of these diseases depends on early detection and administration of effective treatment therefore any diagnostic delay is a huge challenge to curbing these diseases. Hence, there is a need for alternative diagnostic tools, discovery and development of novel therapeutic agents. Studies have demonstrated that aptamers could potentially offer one of the best solutions to these problems. Aptamers are short sequences of either DNA or RNA molecules, which are identified in vitro through a SELEX process. They are sensitive and bind specifically to target molecules. Their promising features suggest they may serve as better diagnostic agents and can be used as drug carriers for therapeutic purposes. In this article, we review the applications of aptamers in the theranostics of cancer and some infectious diseases. Full article
(This article belongs to the Special Issue Aptamer-Based Diagnostics and Therapeutics)
23 pages, 3619 KiB  
Review
Aptamers as Diagnostic Tools in Cancer
by Dario Ruiz Ciancio, Mauricio R. Vargas, William H. Thiel, Martin A. Bruno, Paloma H. Giangrande and María Belén Mestre
Pharmaceuticals 2018, 11(3), 86; https://doi.org/10.3390/ph11030086 - 11 Sep 2018
Cited by 64 | Viewed by 8084
Abstract
Cancer is the second leading cause of death worldwide. Researchers have been working hard on investigating not only improved therapeutics but also on early detection methods, both critical to increasing treatment efficacy, and developing methods for disease prevention. The use of nucleic acids, [...] Read more.
Cancer is the second leading cause of death worldwide. Researchers have been working hard on investigating not only improved therapeutics but also on early detection methods, both critical to increasing treatment efficacy, and developing methods for disease prevention. The use of nucleic acids, or aptamers, has emerged as more specific and accurate cancer diagnostic and therapeutic tools. Aptamers are single-stranded DNA or RNA molecules that recognize specific targets based on unique three-dimensional conformations. Despite the fact aptamer development has been mainly restricted to laboratory settings, the unique attributes of these molecules suggest their high potential for clinical advances in cancer detection. Aptamers can be selected for a wide range of targets, and also linked with an extensive variety of diagnostic agents, via physical or chemical conjugation, to improve previously-established detection methods or to be used as novel biosensors for cancer diagnosis. Consequently, herein we review the principal considerations and recent updates in cancer detection and imaging through aptamer-based molecules. Full article
(This article belongs to the Special Issue Aptamer-Based Diagnostics and Therapeutics)
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Graphical abstract

13 pages, 1827 KiB  
Review
pH-Control in Aptamer-Based Diagnostics, Therapeutics, and Analytical Applications
by Micaela Belleperche and Maria C. DeRosa
Pharmaceuticals 2018, 11(3), 80; https://doi.org/10.3390/ph11030080 - 26 Aug 2018
Cited by 34 | Viewed by 5025
Abstract
Aptamer binding has been used effectively for diagnostics, in-vivo targeting of therapeutics, and the construction and control of nanomachines. Nanostructures that respond to pH by releasing or changing affinity to a target have also been used for in vivo delivery, and in the [...] Read more.
Aptamer binding has been used effectively for diagnostics, in-vivo targeting of therapeutics, and the construction and control of nanomachines. Nanostructures that respond to pH by releasing or changing affinity to a target have also been used for in vivo delivery, and in the construction of sensors and re-usable nanomachines. There are many applications that use aptamers together with pH-responsive materials, notably the targeted delivery of chemotherapeutics. However, the number of reported applications that directly use pH to control aptamer binding is small. In this review, we first discuss the use of aptamers with pH-responsive nanostructures for chemotherapeutic and other applications. We then discuss applications that use pH to denature or otherwise disrupt the binding of aptamers. Finally, we discuss motifs using non-canonical nucleic acid base pairing that can shift conformation in response to pH, followed by an overview of engineered pH-controlled aptamers designed using those motifs. Full article
(This article belongs to the Special Issue Aptamer-Based Diagnostics and Therapeutics)
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14 pages, 1499 KiB  
Review
Nucleic Acid Aptamers Targeting Epigenetic Regulators: An Innovative Therapeutic Option
by Silvia Catuogno, Carla Lucia Esposito, Paola Ungaro and Vittorio De Franciscis
Pharmaceuticals 2018, 11(3), 79; https://doi.org/10.3390/ph11030079 - 24 Aug 2018
Cited by 9 | Viewed by 3930
Abstract
Epigenetic mechanisms include DNA methylation, posttranslational modifications of histones, chromatin remodeling factors, and post transcriptional gene regulation by noncoding RNAs. All together, these processes regulate gene expression by changing chromatin organization and DNA accessibility. Targeting enzymatic regulators responsible for DNA and chromatin modifications [...] Read more.
Epigenetic mechanisms include DNA methylation, posttranslational modifications of histones, chromatin remodeling factors, and post transcriptional gene regulation by noncoding RNAs. All together, these processes regulate gene expression by changing chromatin organization and DNA accessibility. Targeting enzymatic regulators responsible for DNA and chromatin modifications hold promise for modulating the transcriptional regulation of genes that are involved in cancer, as well as in chronic noncommunicable metabolic diseases like obesity, diabetes, and cardiovascular diseases. Increasingly studies are emerging, leading to the identification of specific and effective molecules targeting epigenetic pathways involved in disease onset. In this regard, RNA interference, which uses small RNAs to reduce gene expression and nucleic acid aptamers are arising as very promising candidates in therapeutic approach. Common to all these strategies is the imperative challenge of specificity. In this regard, nucleic acid aptamers have emerged as an attractive class of carrier molecules due to their ability to bind with high affinity to specific ligands, their high chemical flexibility as well as tissue penetration capability. In this review, we will focus on the recent progress in the field of aptamers used as targeting moieties able to recognize and revert epigenetics marks involved in diseases onset. Full article
(This article belongs to the Special Issue Aptamer-Based Diagnostics and Therapeutics)
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16 pages, 7964 KiB  
Review
Targeted Molecular Imaging Using Aptamers in Cancer
by Sorah Yoon and John J. Rossi
Pharmaceuticals 2018, 11(3), 71; https://doi.org/10.3390/ph11030071 - 19 Jul 2018
Cited by 31 | Viewed by 5264
Abstract
Imaging is not only seeing, but also believing. For targeted imaging modalities, nucleic acid aptamers have features such as superior recognition of structural epitopes and quick uptake in target cells. This explains the emergence of an evolved new class of aptamers into a [...] Read more.
Imaging is not only seeing, but also believing. For targeted imaging modalities, nucleic acid aptamers have features such as superior recognition of structural epitopes and quick uptake in target cells. This explains the emergence of an evolved new class of aptamers into a wide spectrum of imaging applications over the last decade. Genetically encoded biosensors tagged with fluorescent RNA aptamers have been developed as intracellular imaging tools to understand cellular signaling and physiology in live cells. Cancer-specific aptamers labeled with fluorescence have been used for assessment of clinical tissue specimens. Aptamers conjugated with gold nanoparticles have been employed to develop innovative mass spectrometry tissue imaging. Also, use of chemically conjugated cancer-specific aptamers as probes for non-invasive and high-resolution imaging has been transformative for in vivo imaging in multiple cancers. Full article
(This article belongs to the Special Issue Aptamer-Based Diagnostics and Therapeutics)
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Graphical abstract

7 pages, 1130 KiB  
Review
Potential Inherent Stimulation of the Innate Immune System by Nucleic Acid Aptamers and Possible Corrective Approaches
by John G. Bruno
Pharmaceuticals 2018, 11(3), 62; https://doi.org/10.3390/ph11030062 - 23 Jun 2018
Cited by 23 | Viewed by 5407
Abstract
It is well known that unmethylated 2′-deoxycytidine-phosphate-2′-guanine (CpG) sequences alone or in longer DNA and RNA oligonucleotides can act like pathogen-associated molecular patterns (PAMPs) and trigger the innate immune response leading to deleterious cytokine production via Toll-like receptors (TLRs). Clearly, such CpG or [...] Read more.
It is well known that unmethylated 2′-deoxycytidine-phosphate-2′-guanine (CpG) sequences alone or in longer DNA and RNA oligonucleotides can act like pathogen-associated molecular patterns (PAMPs) and trigger the innate immune response leading to deleterious cytokine production via Toll-like receptors (TLRs). Clearly, such CpG or CpG-containing sequences in aptamers intended for therapy could present very damaging side effects to patients. Previous antisense oligonucleotide developers were faced with the same basic CpG dilemma and devised not only avoidance, but other effective strategies from which current aptamer developers can learn to ameliorate or eliminate damaging CpG effects. These strategies include obvious methylation of cytosines in the aptamer structure, as long as it does not affect aptamer binding in vivo, truncation of the aptamer to its essential binding site, backbone modifications, co-administration of antagonistic or suppressive oligonucleotides, or other novel drugs under development to lessen the toxic CpG effect on innate immunity. Full article
(This article belongs to the Special Issue Aptamer-Based Diagnostics and Therapeutics)
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19 pages, 15125 KiB  
Review
Research Progress on Rolling Circle Amplification (RCA)-Based Biomedical Sensing
by Lide Gu, Wanli Yan, Le Liu, Shujun Wang, Xu Zhang and Mingsheng Lyu
Pharmaceuticals 2018, 11(2), 35; https://doi.org/10.3390/ph11020035 - 21 Apr 2018
Cited by 62 | Viewed by 13741
Abstract
Enhancing the limit of detection (LOD) is significant for crucial diseases. Cancer development could take more than 10 years, from one mutant cell to a visible tumor. Early diagnosis facilitates more effective treatment and leads to higher survival rate for cancer patients. Rolling [...] Read more.
Enhancing the limit of detection (LOD) is significant for crucial diseases. Cancer development could take more than 10 years, from one mutant cell to a visible tumor. Early diagnosis facilitates more effective treatment and leads to higher survival rate for cancer patients. Rolling circle amplification (RCA) is a simple and efficient isothermal enzymatic process that utilizes nuclease to generate long single stranded DNA (ssDNA) or RNA. The functional nucleic acid unit (aptamer, DNAzyme) could be replicated hundreds of times in a short period, and a lower LOD could be achieved if those units are combined with an enzymatic reaction, Surface Plasmon Resonance, electrochemical, or fluorescence detection, and other different kinds of biosensor. Multifarious RCA-based platforms have been developed to detect a variety of targets including DNA, RNA, SNP, proteins, pathogens, cytokines, micromolecules, and diseased cells. In this review, improvements in using the RCA technique for medical biosensors and biomedical applications were summarized and future trends in related research fields described. Full article
(This article belongs to the Special Issue Aptamer-Based Diagnostics and Therapeutics)
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