RNA aptamers targeting cancer stem cell marker CD133

Shigdar, Sarah; Qiao, Liang; Zhou, Shu‐Feng; Xiang, Dongxi; Wang, Tao; Yong, Li; Lim, Lee Yong; Kong, Lingxue; Li, Lianhong; Duan, Wei

doi:10.1016/j.canlet.2012.11.032

Cited by 150 publications

(103 citation statements)

References 58 publications

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“…To study whether the Apt-functionalized bioconjugate could selectively and effectively deliver drugs to colon cancer cells, the HT29 cell line with abundant EpCAM proteins on cell surfaces was chosen as a model, with HEK293T cells that do not express EpCAM as a negative control. 18 Indeed, the binding of Apt-CUR-NPs to HT29 cells was increased when compared with that of control-Apt-CUR-NPs as well as with the EpCAM-negative cell line HEK293T. To complement the results achieved from confocal microscopy, we further quantitatively evaluated the cellular uptake of CUR-NPs and Apt-CUR-NPs in HT29 cells using an HPLC assay to verify the enhancement uptake of Apt-CUR-NPs by colon cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…This particulate pattern is indicative of endocytosis, as we previously showed for the EpCAM Apt upon binding to HT29 cells. 18 Following the demonstration of Apt-CUR-NPs binding to HT29 cells qualitatively using microscopy, we next sought to confirm the differential uptake of the Apt-CUR-NP bioconjugate quantitatively using HPLC. In a 30-minute time course study, the relative cellular uptake of Apt-CUR-NPs was found to be 138.0 pmol per 1×10 6 cells, compared with 86.6 pmol, 107.2 pmol, and 113.6 pmol per 1×10 6 cells for free CUR, control-CUR-NPs, and CUR-NPs, respectively ( Figure 5).…”

Section: Apt-cur-nps Selectively and Effectively Deliver Drugs To Tarmentioning

confidence: 99%

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Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

Li¹,

Xiang²,

Shigdar³

et al. 2014

IJN

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To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt ( P <0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells.

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Section: Discussionmentioning

confidence: 99%

Section: Apt-cur-nps Selectively and Effectively Deliver Drugs To Tarmentioning

confidence: 99%

Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

Li¹,

Xiang²,

Shigdar³

et al. 2014

IJN

Self Cite

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“…For example, CD133-specific aptamers were demonstrated to outperform CD133 antibodies in penetrating tumor spheres. CD133 RNA aptamers could penetrate a tumor sphere and maintain cellular residence for a minimum of 24 h. In contrast, antibodies could not penetrate the tumor sphere core, even at a concentration 300-fold higher than that of aptamers [21].…”

Section: Comparison Of Aptamers Against Antibodiesmentioning

confidence: 97%

The Clinical Application of Aptamers: Future Challenges and Prospects

Song

Zhang

Zhu

et al. 2015

Aptamers Selected by Cell-Selex for Theranostics

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This final chapter attempts to search for reasons to explain why so little progress has been made in the practical clinical application of aptamers and propose potential solutions to the problem. The advantages and limitations of aptamers in clinical settings are first carefully evaluated. It is suggested that in order to increase the clinical application of aptamers, new selection methods are needed to further improve the success rate of aptamer selection and to efficiently generate stable aptamers for in vivo application with low cost. Several new and promising aptamer selection methods are then reviewed. Strategies for improving selection success rate are highlighted. Finally, efforts leading to the selection of stable aptamers and, hence, increasing the potential for the practical use of aptamer-based technology in clinical settings, are discussed.Keywords Aptamer Á Base modification Á Spiegelmer Á Microfluidics Á SELEX IntroductionBased on their unique functions and features, as discussed throughout the chapters of this book, aptamers have been developed over the past 25 years for applications in chemical sensing, clinical diagnosis, targeted drug delivery, and therapy [1][2][3][4][5][6]. Moreover, the utility of aptamers has been amplified by their compatibility with such detection schemes as electrochemistry [7], fluorescence [8,9], colorimetrics [6,[10][11][12], chemiluminescence [13], field effect transistors [14], and surface plasmon resonance (SPR) [15,16]. However, while aptamer development has flourished in the laboratory, the commercialization of aptamers, especially for biomedical applications, has lagged far behind. Since the invention of aptamer

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“…But to our knowledge no aptamer-based approaches for isolation of the GSC have been developed yet. Thus, the development of aptamers targeting CD133 and TNC (56), may pave the way to future approach for GSC isolation. The isolation of GSC from biological fluids, such as cerebrospinal fluid and blood has also not been attempted until recently, due to the fact that these tumours seldom metastasise (57) and/or due to the fact that fast intracranial tumour progression results in patients' death before these can be diagnosed.…”

Section: Glioblastoma Cell Detection and Isolationmentioning

confidence: 99%

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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RNA aptamers targeting cancer stem cell marker CD133

Cited by 150 publications

References 58 publications

Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

The Clinical Application of Aptamers: Future Challenges and Prospects

Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma

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