Nucleic Acid Aptamers as Potential Therapeutic and Diagnostic Agents for Lymphoma

Shum, Ka-To; Zhou, Jiehua; Rossi, John J.

doi:10.4236/jct.2013.44099

Cited by 20 publications

(18 citation statements)

References 124 publications

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“…The aptamer selection process has been developed using Systematic Evolution of Ligands by EXponential enrichment technique (SELEX), which is a progressive-repeated procedure that aims to select high affinity aptamer sequences from a large combinatorial nucleic acid library that can bind specifically to target molecules [ 19 ]. This process involves binding of random sequences to the target of interest, then separation of the bound sequences and amplification of the recovered aptamers by the polymerase chain reaction (PCR) [ 15 , 20 ]. Aptamers have been studied as bio- probes in diverse diagnostic and therapeutic applications as well as in the production of new drugs and improving drug delivery systems [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Selection and targeting of EpCAM protein by ssDNA aptamer

et al. 2017

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Aptamers are molecules that reveal highly complex and refined molecular recognition properties. These molecules are capable of binding with high affinity and selectivity to targets, ranging from small molecules to whole living cells. Several aptamers have been selected for targeting cellular proteins and they have also used in developing therapeutics and diagnostic strategies. Epithelial cell adhesion molecule (EpCAM) is considered as a cancer stem cell (CSC) biomarker and one of the most promising targets for aptamer selection against CSCs. In this study, we have developed a ssDNA aptamer with high affinity and selectivity of targeting the EpCAM protein extracellular domain. The SELEX technique was applied and the resulted sequences were tested on EpCAM-positive human gastric cancer cell line, KATO III, and the EpCAM-negative mouse embryonic fibroblast, NIH/3T3 cells. Ep1 aptamer was successfully isolated and showed selective binding on EpCAM-positive KATO III cells when compared to EpCAM-negative NIH/3T3 cells, as observed by the flow cytometry and the confocal imaging results. Additionally, the binding of Ep1 to EpCAM protein was assessed using mobility shifting assay and aptamers-protein docking. Furthermore, the binding affinity of Ep1 was measured against EpCAM protein using EpCAM-immobilized on magnetic beads and showed apparent affinity of 118 nM. The results of this study could suggest that Ep1 aptamer can bind specifically to the cellular EpCAM protein, making it an attractive ligand for targeted drug delivery and as an imaging agent for the identification of cancer cells.

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Section: Introductionmentioning

confidence: 99%

Selection and targeting of EpCAM protein by ssDNA aptamer

et al. 2017

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“…A number of reports describe aptamers specific of tumor markers [ 18 – 19 ]. Such aptamers are used for many different purposes such as biosensing [ 20 ], delivery [ 21 – 22 ], flow-cytometry [ 23 ], diagnostics [ 24 – 25 ] and therapeutics [ 21 , 26 ]. The binding characteristics of aptamers, namely high affinity and specific recognition of the target as well as their easy of synthesis made them excellent candidates for imaging.…”

Section: Introductionmentioning

confidence: 99%

Ex Vivo and In Vivo Imaging and Biodistribution of Aptamers Targeting the Human Matrix MetalloProtease-9 in Melanomas

et al. 2016

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The human Matrix MetalloProtease-9 (hMMP-9) is overexpressed in tumors where it promotes the release of cancer cells thus contributing to tumor metastasis. We raised aptamers against hMMP-9, which constitutes a validated marker of malignant tumors, in order to design probes for imaging tumors in human beings. A chemically modified RNA aptamer (F3B), fully resistant to nucleases was previously described. This compound was subsequently used for the preparation of F3B-Cy5, F3B-S-acetylmercaptoacetyltriglycine (MAG) and F3B-DOTA. The binding properties of these derivatives were determined by surface plasmon resonance and electrophoretic mobility shift assay. Optical fluorescence imaging confirmed the binding to hMMP-9 in A375 melanoma bearing mice. Quantitative biodistribution studies were performed at 30 min, 1h and 2 h post injection of 99mTc-MAG-aptamer and 111In-DOTA-F3B. 99mTc radiolabeled aptamer specifically detected hMMP-9 in A375 melanoma tumors but accumulation in digestive tract was very high. Following i.v. injection of 111In-DOTA-F3B, high level of radioactivity was observed in kidneys and bladder but digestive tract uptake was very limited. Tumor uptake was significantly (student t test, p<0.05) higher for 111In-DOTA-F3B with 2.0%ID/g than for the 111In-DOTA-control oligonucleotide (0.7%ID/g) with tumor to muscle ratio of 4.0. Such difference in tumor accumulation has been confirmed by ex vivo scintigraphic images performed at 1h post injection and by autoradiography, which revealed the overexpression of hMMP-9 in sections of human melanomas. These results demonstrate that F3B aptamer is of interest for detecting hMMP-9 in melanoma tumor.

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“…Furthermore, due to the possibility of multiple targets on the cell surface, additional characterization is necessary to find an appropriate target. Selection should be carried out against live cells, as dead cells have higher chances of losing membrane integrity (Shum et al 2013). Cell-SELEX currently plays a major role in the field of oncology, where its major advantage is that there is no need to purify the surface antigen because aptamers can be generated via native selection.…”

Section: Cell-selexmentioning

confidence: 99%

“…5a, b). Shum et al (2013) used the term Bsmart bomb^to describe the role of aptamers in selectively killing targets. Based on internalization, an uptake selection was performed against prostate cancer that can differentiate it from non-prostate cancers.…”

Section: Aptamers As Cell Surface Targeting and Intracellular Delivermentioning

confidence: 99%

Cell-targeting aptamers act as intracellular delivery vehicles

Gopinath

Lakshmipriya

Chen

et al. 2016

Appl Microbiol Biotechnol

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Aptamers are single-stranded nucleic acids or peptides identified from a randomized combinatorial library through specific interaction with the target of interest. Targets can be of any size, from small molecules to whole cells, attesting to the versatility of aptamers for binding a wide range of targets. Aptamers show drug properties that are analogous to antibodies, with high specificity and affinity to their target molecules. Aptamers can penetrate disease-causing microbial and mammalian cells. Generated aptamers that target surface biomarkers act as cell-targeting agents and intracellular delivery vehicles. Within this context, the "cell-internalizing aptamers" are widely investigated via the process of cell uptake with selective binding during in vivo systematic evolution of ligands by exponential enrichment (SELEX) or by cell-internalization SELEX, which targets cell surface antigens to be receptors. These internalizing aptamers are highly preferable for the localization and functional analyses of multiple targets. In this overview, we discuss the ways by which internalizing aptamers are generated and their successful applications. Furthermore, theranostic approaches featuring cell-internalized aptamers are discussed with the purpose of analyzing and diagnosing disease-causing pathogens.

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Nucleic Acid Aptamers as Potential Therapeutic and Diagnostic Agents for Lymphoma

Cited by 20 publications

References 124 publications

Selection and targeting of EpCAM protein by ssDNA aptamer

Selection and targeting of EpCAM protein by ssDNA aptamer

Ex Vivo and In Vivo Imaging and Biodistribution of Aptamers Targeting the Human Matrix MetalloProtease-9 in Melanomas

Cell-targeting aptamers act as intracellular delivery vehicles

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