DNA aptamers that target human glioblastoma multiforme cells overexpressing epidermal growth factor receptor variant III in vitro

Tan, Yan; Shi, Yusheng; Wu, Xidong; Liang, Hang; Gao, Yubo; Li, Shu-Ji; Zhang, Xingmei; Wang, Fang; Gao, Tianming

doi:10.1038/aps.2013.137

Cited by 46 publications

(29 citation statements)

References 30 publications

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“…Likewise, the aptamers designated U2, U8, 32, 41, 43, and 47 specifically binding to U87-MG EGFRvIII positive U87-MG cells, but not to nonmutated ones, were generated by the cell-SELEX method. The specificity of the U2 and U8 aptamers for EGFRvIII binding was established with time dependent protease-K treatment of the cells, followed by flow cytometry analysis, as described by Tan et al (26). The targeted common mutation of EGFR, the EGFRvIII is associated with worse survival of the patients with primary glioblastoma (28).…”

Section: Cell-selex Against Known Specific Glioblastoma Markersmentioning

confidence: 99%

“…Contrary, when they were injected intratumorally, they were shown to retained aptamers for only half an hour, being totally eliminated after three hours. High-density image of these aptamers later revealed their accumulation in the bladder, implying on their major excretion via urinary tract (26).…”

Section: Clinical Applications Of Aptamers Imagingmentioning

confidence: 99%

“…For example, 188 Re-labeled U2 aptamer complexes, injected intravenously into tumour bearing mice, accumulated in their EGFRvIII-expressing xenografts, thus proving as a promising tool for GBM imaging and diagnosis. Moreover, this radioactive aptamer tracer may serve also for imaging other malignancies with EGFRvIII overexpression (26).…”

Section: Clinical Applications Of Aptamers Imagingmentioning

confidence: 99%

“…Aptamers have been developed for flow cytometric identification of various tumor cells, such as small cell lung cancer, breast and gastric cancers, acute myelogenous leukemia and glioblastoma among further examples (21,26,(47)(48)(49)(50)(51).…”

Section: Flow and Image Cytometry And Aptamersmentioning

confidence: 99%

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Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma

Delač

Motaln

Ulrich³

et al. 2015

Cytometry Pt A

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Aptamers are short single-stranded nucleic acids (RNA or ssDNA), identified by an in vitro selection process, denominated SELEX, from a partially random oligonucleotide library. They bind to a molecular target, a protein or other complex macromolecular structures of interest with high affinity and specificity, comparable to those of antibodies. Recently, aptamer selection protocols were developed for targeting living cells, including tumors. Chemical modifications of the aptamers and modalities of their detection and delivery systems are already available with high selectivity and targeting ability for the desired cancer cell type, making them promising for diagnosis and therapy. Glioblastoma multiformae represents the most malignant and fatal stage of glioma, and is also the most frequent brain tumor. Glioblastoma-specific aptamers were developed by either targeting the whole cell surface or known glioma biomarkers. These aptamers may gain importance for imaging, tumor cell isolation from biopsies and drug delivery. In biomedical imaging techniques, aptamers coupled with radionuclide or fluorescent labels, bioconjugates and nanoparticles offer an advanced, noninvasive manner for defining the glioblastoma tissue border. Though single modality aptamer imaging probes have some limitations, these are overcome by the use of multimodal probes. Due to selectivity and chemical characteristics, aptamers can be coupled to functionalized nanoparticles and loaded with a drug, appeared promising for in vivo targeting of glioblastoma. Finally, aptamers are effective mediators for gene silencing when coupled to small interfering RNA and a viral vector, thus providing a novel tool with enhanced targeting capability in drug delivery, designed for tailored treatment of glioblastoma patients. V C 2015 International Society for Advancement of Cytometry Key terms aptamer; SELEX; cancer biomarkers; cell and target protein; imaging; drug delivery; glioblastoma; nanoparticles APTAMERS AND THE SELEX TECHNOLOGY IN CANCER APTAMERS, first introduced by Tuerk and Gold (1) and Ellington and Szostak (2), are short chains of DNA or RNA oligonucleotides that bind to small molecules, peptides, and macromolecules, such as proteins of various sizes and conformations. These are identified by an in vitro selection method in a stepwise evolutionary process from a combinatorial library of partial randomized oligonucleotides, consisting of up to 10 15 different sequences and secondary and tertiary structures by a method called SELEX (Systematic Evolution of Ligands by EXponential enrichment). It begins with a pool of variable oligonucleotide sequences with multiple rounds of target exposure of the combinatorial RNA or DNA library, followed by elution of target binders and enrichment of those by RT-PCR or PCR procedures are performed. These results in exponential increase of oligonucleotides with improved ligand to target binding in the previously combinatorial library, which finally is narrowed down to a homogeneous population of high-affinity...

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Section: Cell-selex Against Known Specific Glioblastoma Markersmentioning

confidence: 99%

Section: Clinical Applications Of Aptamers Imagingmentioning

confidence: 99%

Section: Clinical Applications Of Aptamers Imagingmentioning

confidence: 99%

Section: Flow and Image Cytometry And Aptamersmentioning

confidence: 99%

See 2 more Smart Citations

Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma

Delač

Motaln

Ulrich³

et al. 2015

Cytometry Pt A

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“…34,35 Compared with RNA aptamers, DNA aptamers are more stable and cheaper to synthesize. A32 (DNA), which specially binds to EGFRvIII protein, was first discovered by Tan et al 36 and then used to conjugate small interfering RNA and deliver it into U87-EGFRvIII cells. 37 To overcome the disadvantages of conventional fluorophores and implement the maximum safe resection, this study engineered a nanoprobe, biotin-aptamer-conjugated streptavidin-PEG-CdSe/ZnS QDs (QD-Apt), for preoperative diagnosis, intraoperative resection, and postoperative examination of glioma.…”

mentioning

confidence: 99%

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma

Tang¹,

Huang²,

Zhang³

et al. 2017

IJN

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The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs) were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling glioma cell lines and human brain glioma tissues, and target gliomas in situ was also investigated. We found that not only could QD-Apt specially bind to the U87-EGFRvIII glioma cells but also bind to human glioma tissues in vitro. Fluorescence imaging in vivo with orthotopic glioma model mice bearing U87-EGFRvIII showed that QD-Apt could penetrate the blood–brain barrier and then selectively accumulate in the tumors through binding to EGFRvIII, and consequently, generate a strong fluorescence, which contributed to the margins of gliomas that were visualized clearly, and thus, help the surgeons realize the maximum safe resection of glioma. In addition, QD-Apt can also be applied in preoperative diagnosis and postoperative examination of glioma. Therefore, these achievements facilitate the use of tumor-targeted fluorescence imaging in the diagnosis, surgical resection, and postoperative examination of glioma.

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A Targeted Nano Drug Delivery System of AS1411 Functionalized Graphene Oxide Based Composites

et al. 2021

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A novel method for the preparation of antitumor drug vehicles has been optimized. Biological materials of chitosan oligosaccharide (CO) and γ-polyglutamic acid (γ-PGA) have previously been employed as modifiers to covalently modify graphene oxide (GO), which in turn loaded doxorubicin (DOX) to obtain a nano drug delivery systems of graphene oxide based composites (GO-CO-γ-PGA-DOX). The system was not equipped with the ability of initiative targeting, thus resulting into toxicity and side effects on normal tissues or organs. In order to further improve the targeting property of the system, the nucleic acid aptamer NH 2 -AS1411 (APT) of targeted nucleolin (C23) was used to conjugate on GO-CO-γ-PGA to yield the targeted nano drug delivery system APT-GO-CO-γ-PGA. The structure, composition, dispersion, particle size and morphology properties of the synthesized complex have been studied using multiple characterization methods. Drug loading and release profile data showed that APT-GO-CO-γ-PGA is provided with high drug loading capacity and is capable of controlled and sustained release of DOX. Cell experimental results indicated that since C23 was overexpressed on the surface of Hela cells but not on the surface of Beas-2B cells, APT-GO-CO-γ-PGA-DOX can target Hela cells and make increase toxicity to Hela cells than Beas-2B cells, and the IC 50 value of APT-GO-CO-γ-PGA-DOX was 3.23 � 0.04 μg/mL. All results proved that APT-GO-CO-γ-PGA can deliver antitumor drugs in a targeted manner, and achieve the effect of reducing poison, which indicated that the targeted carrier exhibits a broad application prospect in the field of biomedicine.

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DNA aptamers that target human glioblastoma multiforme cells overexpressing epidermal growth factor receptor variant III in vitro

Abstract: The DNA aptamers are promising molecular probes for the diagnosis and treatment of GBM.

Cited by 46 publications

References 30 publications

Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma

Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma

A Targeted Nano Drug Delivery System of AS1411 Functionalized Graphene Oxide Based Composites

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