Gint4.T-Modified DNA Tetrahedrons Loaded with Doxorubicin Inhibits Glioma Cell Proliferation by Targeting PDGFRβ

Wang, Feng; Zhou, Yanghao; Cheng, Sheue-yann; Lou, Jinhe; Zhang, Xiang; He, Qiuguang; Huang, Ning; Yuan, Chao

doi:10.1186/s11671-020-03377-y

Cited by 28 publications

(19 citation statements)

References 31 publications

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“…Indeed, the PDGFRβ Gint4.T aptamer successfully delivered PLGA-b-PEG PNPs loaded with the low-water-soluble NVP-BEZ235 drug to GBM intracranially implanted in mice [117]. More recently, Gint4.T was assembled into tetrahedral DNA nanostructures, alone [118] or in combination with the GMT8 aptamer [107], to deliver doxorubicin or paclitaxel to GBM cells, respectively, by crossing in vitro models of BBB.…”

Section: Cl4 Gint4t and Gl21t Aptamersmentioning

confidence: 99%

Profiling Cancer Cells by Cell-SELEX: Use of Aptamers for Discovery of Actionable Biomarkers and Therapeutic Applications Thereof

et al. 2021

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The identification of tumor cell-specific surface markers is a key step towards personalized cancer medicine, allowing early assessment and accurate diagnosis, and development of efficacious targeted therapies. Despite significant efforts, currently the spectrum of cell membrane targets associated with approved treatments is still limited, causing an inability to treat a large number of cancers. What mainly limits the number of ideal clinical biomarkers is the high complexity and heterogeneity of several human cancers and still-limited methods for molecular profiling of specific cancer types. Thanks to the simplicity, versatility and effectiveness of its application, cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technology is a valid complement to the present strategies for biomarkers’ discovery. We and other researchers worldwide are attempting to apply cell-SELEX to the generation of oligonucleotide aptamers as tools for both identifying new cancer biomarkers and targeting them by innovative therapeutic strategies. In this review, we discuss the potential of cell-SELEX for increasing the currently limited repertoire of actionable cancer cell-surface biomarkers and focus on the use of the selected aptamers as components of innovative conjugates and nano-formulations for cancer therapy.

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Section: Cl4 Gint4t and Gl21t Aptamersmentioning

confidence: 99%

Profiling Cancer Cells by Cell-SELEX: Use of Aptamers for Discovery of Actionable Biomarkers and Therapeutic Applications Thereof

et al. 2021

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“…[178] The RNA aptamer Gint4.T was found to cross the bloodbrain barrier and therefore serves as a promising candidate for the treatment of brain tumor, e.g., glioblastoma multiforme. [170,180,181] Nanoparticle conjugates with Gint4.T consisting of TDNs and Gint4.T or Gint4.T in combination with GMT8 DNA aptamer, which has a high specificity for U87MG glioblastoma cells, were loaded with DOX [182] and PTX. [181] Both constructs showed enhanced uptake into and cytotoxicity against U87MG cells for DOX, inhibiting the cell cycle and proliferation (DOX) and promoting apoptosis (PTX).…”

Section: Aptamersmentioning

confidence: 99%

Prospective Cancer Therapies Using Stimuli‐Responsive DNA Nanostructures

Seitz

Ahmed

Nurmi

et al. 2021

Macromolecular Bioscience

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Nanostructures based on DNA self-assembly present an innovative way to address the increasing need for target-specific delivery of therapeutic molecules. Currently, most of the chemotherapeutics being used in clinical practice have undesired and exceedingly high off-target toxicity. This is a challenge in particular for small molecules, and hence, developing robust and effective methods to lower these side effects and enhance the antitumor activity is of paramount importance. Prospectively, these issues could be tackled with the help of DNA nanotechnology, which provides a route for the fabrication of custom, biocompatible, and multimodal structures, which can, to some extent, resist nuclease degradation and survive in the cellular environment. Similar to widely employed liposomal products, the DNA nanostructures (DNs) are loaded with selected drugs, and then by employing a specific stimulus, the payload can be released at its target region. This review explores several strategies and triggers to achieve targeted delivery of DNs. Notably, different modalities are explained through which DNs can interact with their respective targets as well as how structural changes triggered by external stimuli can be used to achieve the display or release of the cargo. Furthermore, the prospects and challenges of this technology are highlighted.

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“…19 It can be rapidly self-assembled from four designed single-strand DNA (ssDNA) via Watson-Crick base pairing. 20 To synthesize As-TDN-R previously reported methods were used with slight modifications 21 as shown in Table 1. AS1411 aptamer was strengthened on the 5ʹ end of s1, and the complementary strand of siRNA-R on s2.…”

Section: Synthesis and Characterization Of As-tdn-rmentioning

confidence: 99%

Self-Assembled DNA Nanostructure as a Carrier for Targeted siRNA Delivery in Glioma Cells

Zhou

Yang

Wang

et al. 2021

IJN

Self Cite

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Introduction RNA interference is a promising therapy in glioma treatment. However, the application of RNA interference has been limited in glioma therapy by RNA instability and the lack of tumor targeting. Here, we report a novel DNA tetrahedron, which can effectively deliver small interfering RNA to glioma cells and induce apoptosis. Methods siRNA, a small interfering RNA that can suppress the expression of survivin in glioma, was loaded into the DNA tetrahedron (TDN). To enhance the ability of active targeting of this nanoparticle, we modified one side of the DNA nanostructure with aptamer as1411 (As-TDN-R), which can selectively recognize the nucleolin in the cytomembrane of tumor cells. The modified nanoparticles were characterized by agarose gel electrophoresis, dynamic light scattering, and transmission electron microscopy. The serum stability was evaluated by agarose gel electrophoresis. Nucleolin was detected by Western blot and immunofluorescence, and targeted cellular uptake was examined by flow cytometry. The TUNEL assay, flow cytometry, and Western Blot were used to detect apoptosis in U87 cells. The gene silencing of survivin was examined by qPCR, Western Blot, and immunofluorescence. Results As-TDN-R alone showed better stability towards siRNA, indicating that TDN was a good siRNA protector. Compared with TDN alone, there was increased intercellular uptake of As-TDN-R by U87 cells, evidenced by overexpressed nucleolin in glioma cell lines. TUNEL assay, flow cytometry, and Western Blot revealed increased apoptosis in the As-TDN-R group. The downregulation of survivin protein and mRNA expression levels indicated that As-TDN-R effectively silenced the target gene. Conclusion The novel nanoparticle can serve as a good carrier for targeting siRNA delivery in glioma. Further exploration of the DNA nanostructure can greatly promote the application of DNA-based drug systems in glioma.

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Gint4.T-Modified DNA Tetrahedrons Loaded with Doxorubicin Inhibits Glioma Cell Proliferation by Targeting PDGFRβ

Cited by 28 publications

References 31 publications

Profiling Cancer Cells by Cell-SELEX: Use of Aptamers for Discovery of Actionable Biomarkers and Therapeutic Applications Thereof

Profiling Cancer Cells by Cell-SELEX: Use of Aptamers for Discovery of Actionable Biomarkers and Therapeutic Applications Thereof

Prospective Cancer Therapies Using Stimuli‐Responsive DNA Nanostructures

Self-Assembled DNA Nanostructure as a Carrier for Targeted siRNA Delivery in Glioma Cells

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