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Aptamer-Mediated Cancer Theranostics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 20440

Special Issue Editor

Special Issue Information

Dear Colleagues,

Aptamers have emerged as a new generation of bioaffinity ligands with enhanced target binding specificity and selectivity. They possess high binding affinities with nano- to pico- molar dissociation constants, enabling various biomedical applications relating to molecular targeting and recognition via hydrogen bonding, Van Der Waal forces and electrostatic interactions. Aptamers are non-viral oligonucleotides and can be generated via Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Recent research has focused on the use of aptamers in cancer diagnostics and targeted therapy applications, owing to their attractive biophysical and biochemical features including bioavailability, biocompatibility, stability and low immunogenicity.

This special issue seeks to create a platform that will stimulate the continuing efforts of developing aptamer-based techniques for cancer theranostic applications. Research contributions to this special issue may include but are not limited to the generation of aptamer via novel SELEX methods; advanced approaches for aptamer characterization; interactions and characterizations of aptamer-biomarker binding; aptameric nanosensors for cancer detection; and in silico approaches such as structural modeling and molecular dynamics simulation for aptamer-receptor binding analysis.

Dr. Michael Danquah
Guest Editor

Manuscript Submission Information

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Keywords

  • Aptamer
  • Cancer
  • Diagnostics
  • Therapy
  • Receptor
  • Bionanosensor
  • Biomarker
  • Nanomedicine

Published Papers (6 papers)

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Editorial

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3 pages, 166 KiB  
Editorial
Editorial to the IJMS Special Issue “Aptamer-Mediated Cancer Theranostics”
by Michael K. Danquah
Int. J. Mol. Sci. 2023, 24(8), 7253; https://doi.org/10.3390/ijms24087253 - 14 Apr 2023
Cited by 1 | Viewed by 873
Abstract
Aptamers have emerged as a new generation of bioaffinity probes with enhanced target binding specificity and selectivity [...] Full article
(This article belongs to the Special Issue Aptamer-Mediated Cancer Theranostics)

Research

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13 pages, 2261 KiB  
Article
Development of HER2-Specific Aptamer-Drug Conjugate for Breast Cancer Therapy
by Hwa Yeon Jeong, Hyeri Kim, Myunghwa Lee, Jinju Hong, Joo Han Lee, Jeonghyeon Kim, Moon Jung Choi, Yong Serk Park and Sung-Chun Kim
Int. J. Mol. Sci. 2020, 21(24), 9764; https://doi.org/10.3390/ijms21249764 - 21 Dec 2020
Cited by 20 | Viewed by 4681
Abstract
In this study, HER2 RNA aptamers were conjugated to mertansine (DM1) and the anti-cancer effectiveness of the conjugate was evaluated in HER2-overexpressing breast cancer models. The conjugate of HER2 aptamer and anticancer drug DM1 (aptamer-drug conjugate, ApDC) was prepared and analyzed using HPLC [...] Read more.
In this study, HER2 RNA aptamers were conjugated to mertansine (DM1) and the anti-cancer effectiveness of the conjugate was evaluated in HER2-overexpressing breast cancer models. The conjugate of HER2 aptamer and anticancer drug DM1 (aptamer-drug conjugate, ApDC) was prepared and analyzed using HPLC and mass spectrometry. The cell-binding affinity and cytotoxicity of the conjugate were determined using confocal microscopy and WST-1 assay. The in vivo anti-tumoral efficacy of ApDC was also evaluated in mice carrying BT-474 breast tumors overexpressing HER2. The synthesized HER2-specific RNA aptamers were able to specifically and efficiently bind to HER-positive BT-474 breast cancer cells, but not to HER2-negative MDA-MB-231 breast cancer cells. Also, the HER2-specific ApDC showed strong toxicity to the target cells, BT-474, but not to MDA-MB-231 cells. According to the in vivo analyses drawn from the mouse xenografts of BT-747 tumor, the ApDC was able to more effectively inhibit the tumor growth. Compared to the control group, the mice treated with the ApDC showed a significant reduction of tumor growth. Besides, any significant body weight losses or hepatic toxicities were monitored in the ApDC-treated mice. This research suggests the HER2 aptamer-DM1 conjugate as a target-specific anti-cancer modality and provides experimental evidence supporting its enhanced effectiveness for HER2-overexpressing target tumors. This type of aptamer-conjugated anticancer drug would be utilized as a platform structure for the development of versatile targeted high-performance anticancer drugs by adopting the easy deformability and high affinity of aptamers. Full article
(This article belongs to the Special Issue Aptamer-Mediated Cancer Theranostics)
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12 pages, 2256 KiB  
Article
Therapeutic Application of Drug-Conjugated HER2 Oligobody (HER2-DOligobody)
by Hyun Jung Kim, Ho Jin Sung, Yul Min Lee, Sun Il Choi, Yun-Hee Kim, Kyun Heo and In-Hoo Kim
Int. J. Mol. Sci. 2020, 21(9), 3286; https://doi.org/10.3390/ijms21093286 - 06 May 2020
Cited by 5 | Viewed by 3126
Abstract
Antibody drug conjugates (ADCs), consisting of a cancer-specific antibody and cytotoxic payload, are shown to be a potent class of anticancer therapeutics, with enhanced therapeutic efficacy and reduced “off-target” side effects. However, the therapeutic window of ADCs is narrowed by problems such as [...] Read more.
Antibody drug conjugates (ADCs), consisting of a cancer-specific antibody and cytotoxic payload, are shown to be a potent class of anticancer therapeutics, with enhanced therapeutic efficacy and reduced “off-target” side effects. However, the therapeutic window of ADCs is narrowed by problems such as difficulty in site-specific conjugation of payload, changes in antibody stability due to payload conjugation, and difficulty in tissue penetration. In this respect, aptamers have advantages in drug-delivery, as they can be easily and stably conjugated with cytotoxic drugs. We previously reported that oligobody, an aptamer-antibody complex, is a novel delivery method for aptamer-based therapeutics. In the current study, we describe DOligobody, a drug-conjugated oligobody comprising an aptamer-drug conjugate and an antibody. A cotinine-conjugated anti-HER2 aptamer (cot-HER2apt) was specifically bound to HER2-positive NCI-N87 cells, and underwent receptor-mediated endocytosis. Further, HER2-DOligobody, a cot-HER2apt-conjugated monomethyl auristatin E (cot-HER2apt-MMAE) oligobody, inhibited the growth of HER2-positive NCI-N87 cells. Finally, systemic administration of HER2-DOligobody significantly reduced tumor growth in a xenograft mouse model. Taken together, these results suggest that our DOligobody strategy may be a powerful platform for rapid, low-cost and effective cancer therapy. Full article
(This article belongs to the Special Issue Aptamer-Mediated Cancer Theranostics)
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Review

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13 pages, 869 KiB  
Review
Neuroblastoma GD2 Expression and Computational Analysis of Aptamer-Based Bioaffinity Targeting
by Godfred O. Sabbih and Michael K. Danquah
Int. J. Mol. Sci. 2021, 22(16), 9101; https://doi.org/10.3390/ijms22169101 - 23 Aug 2021
Cited by 7 | Viewed by 3110
Abstract
Neuroblastoma (NB) is a neuroectodermal embryonic cancer that originates from primordial neural crest cells, and amongst pediatric cancers with high mortality rates. NB is categorized into high-, intermediate-, and low-risk cases. A significant proportion of high-risk patients who achieve remission have a minimal [...] Read more.
Neuroblastoma (NB) is a neuroectodermal embryonic cancer that originates from primordial neural crest cells, and amongst pediatric cancers with high mortality rates. NB is categorized into high-, intermediate-, and low-risk cases. A significant proportion of high-risk patients who achieve remission have a minimal residual disease (MRD) that causes relapse. Whilst there exists a myriad of advanced treatment options for NB, it is still characterized by a high relapse rate, resulting in a reduced chance of survival. Disialoganglioside (GD2) is a lipo-ganglioside containing a fatty acid derivative of sphingosine that is coupled to a monosaccharide and a sialic acid. Amongst pediatric solid tumors, NB tumor cells are known to express GD2; hence, it represents a unique antigen for subclinical NB MRD detection and analysis with implications in determining a response for treatment. This article discusses NB MRD expression and analytical assays for GD2 detection and quantification as well as computational approaches for GD2 characterization based on high-throughput image processing and genomic data analysis. Full article
(This article belongs to the Special Issue Aptamer-Mediated Cancer Theranostics)
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20 pages, 2269 KiB  
Review
The Potential of Aptamer-Mediated Liquid Biopsy for Early Detection of Cancer
by Dhruvajyoti Roy, Andreas Pascher, Mazen A. Juratli and Judith C. Sporn
Int. J. Mol. Sci. 2021, 22(11), 5601; https://doi.org/10.3390/ijms22115601 - 25 May 2021
Cited by 22 | Viewed by 3966
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Aptamer-Mediated Cancer Theranostics)
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27 pages, 2187 KiB  
Review
Advances in Oligonucleotide Aptamers for NSCLC Targeting
by Deborah Rotoli, Laura Santana-Viera, Maria L. Ibba, Carla L. Esposito and Silvia Catuogno
Int. J. Mol. Sci. 2020, 21(17), 6075; https://doi.org/10.3390/ijms21176075 - 23 Aug 2020
Cited by 8 | Viewed by 3945
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Aptamer-Mediated Cancer Theranostics)
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