EpCAM Aptamer-mediated Survivin Silencing Sensitized Cancer Stem Cells to Doxorubicin in a Breast Cancer Model

Wang, Tao; Gantier, Michael P.; Xiang, Dongxi; Bean, Andrew G.D.; Bruce, Matthew P.; Zhou, Shu‐Feng; Khasraw, Mustafa; Ward, Alister C.; Wang, Li; Wei, Ming Q.; AlShamaileh, Hadi; Chen, Lijue; She, Xiaodong; Ji, Lin; Kong, Lingxue; Shigdar, Sarah; Duan, Wei

doi:10.7150/thno.11692

Cited by 90 publications

(61 citation statements)

References 58 publications

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“…In this regard, several shortened aptamers have been proposed with different analytes (Gopinath et al 2006a), as smaller aptamers perform better as chimeras because longer aptamers may undergo degradation. In recent years, there has been an increasing interest in the applications of aptamer chimeras in the field of therapeutics Rohde et al 2015;Subramanian et al 2015;Wang et al 2015;Diao et al 2016). Rohde et al (2015) demonstrated a transferrin receptor and microRNA aptamer chimera (mir-126) that promoted sprouting of endothelial cells and suppressed recruitment of breast cancer cells.…”

Section: Aptamer-based Chimerasmentioning

confidence: 99%

“…Rohde et al (2015) demonstrated a transferrin receptor and microRNA aptamer chimera (mir-126) that promoted sprouting of endothelial cells and suppressed recruitment of breast cancer cells. An aptamersiRNA polymeric nanocomplex was designed for targeting epithelial cell adhesion molecules, which are overexpressed in solid tumors (Subramanian et al 2015), and Wang et al (2015) used the aptamer-siRNA chimera to silence survivin in cancer cells and enhance the effect of doxorubicin, even when used in small amounts. Very recently, using an antiprostate specific membrane antigen aptamer-siRNA chimera, Diao et al (2016) specifically controlled the growth of a prostate tumor.…”

Section: Aptamer-based Chimerasmentioning

confidence: 99%

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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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Section: Aptamer-based Chimerasmentioning

confidence: 99%

Section: Aptamer-based Chimerasmentioning

confidence: 99%

Cell-targeting aptamers act as intracellular delivery vehicles

Gopinath

Lakshmipriya

Chen

et al. 2016

Appl Microbiol Biotechnol

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“…In a very aggressive triple-negative breast cancer xenograft model, the EpCAM-AsiC treatment caused complete tumor regression [41]. Further, anti EpCAM aptamer-mediated survivin silencing has been explored to sensitize breast cancer stem cells to Doxorubicin [42]. …”

Section: Aptamer-drug and Oligonucleotide Systemsmentioning

confidence: 99%

Aptamer-Mediated Targeted Delivery of Therapeutics: An Update

2016

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The selective delivery of drugs in a cell- or tissue-specific manner represents the main challenge for medical research; in order to reduce the occurrence of unwanted off-target effects. 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. To date, different aptamer-drug systems and aptamer–nanoparticles systems, in which nanoparticles function together with aptamers for the targeted delivery, have been successfully developed for a wide range of therapeutics, including toxins; peptides; chemotherapeutics and oligonucleotides. Therefore, aptamer-mediated drug delivery represents a powerful tool for the safe and effective treatment of different human pathologies, including cancer; neurological diseases; immunological diseases and so on. In this review, we will summarize recent progress in the field of aptamer-mediated drug delivery and we will discuss the advantages, the achieved objectives and the challenges to be still addressed in the near future, in order to improve the effectiveness of therapies.

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“…The siRNA accumulated at the tumor site and resulted in an 80% knockdown of the survivin gene, which inhibits apoptosis and promotes chemoresistance in CSCs. When combined with doxorubicin, the aptamer-siRNA chimera improved survival rates of tumor-bearing mice, [37] demonstrating the effectiveness of anti-CSC RNAi in vivo …”

Section: Silencing Oncogenesmentioning

confidence: 99%

Therapeutic strategies for targeting cancer stem cells

Kim¹,

Siegler²,

Siriwon³

et al. 2016

JCMT

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The therapeutic limitations of conventional chemotherapeutic drugs present a challenge for cancer therapy; these shortcomings are largely attributed to the ability of cancer cells to repopulate and metastasize after initial therapies. Compelling evidence suggests that cancer stem cells (CSCs) have a crucial impact in current shortcomings of cancer therapy because they are largely responsible for tumor initiation, relapse, metastasis, and chemo-resistance. Thus, a better understanding of the properties and mechanisms underlying CSC resistance to treatments is necessary to improve patient outcomes and survival rates. In this review, the authors characterize and compare different CSC-specific biomarkers that are present in various types of tumors. We further discuss multiple targeting approaches currently in preclinical or clinical testing that show great potential for targeting CSCs. This review discusses numerous strategies to eliminate CSCs by targeting surface biomarkers, regulating CSC-associated oncogenes and signaling pathways, inhibiting drug-efflux pumps involved in drug resistance, modulating the tumor microenvironment and immune system, and applying drug combination therapy using nanomedicine.

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EpCAM Aptamer-mediated Survivin Silencing Sensitized Cancer Stem Cells to Doxorubicin in a Breast Cancer Model

Cited by 90 publications

References 58 publications

Cell-targeting aptamers act as intracellular delivery vehicles

Cell-targeting aptamers act as intracellular delivery vehicles

Aptamer-Mediated Targeted Delivery of Therapeutics: An Update

Therapeutic strategies for targeting cancer stem cells

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