A GSH‐Gated DNA Nanodevice for Tumor‐Specific Signal Amplification of microRNA and MR Imaging–Guided Theranostics

Yan, Nan; Lin, Lin; Xu, Caina; Tian, Huayu; Chen, Xuesi

doi:10.1002/smll.201903016

Cited by 64 publications

(43 citation statements)

References 59 publications

(33 reference statements)

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“…Furthermore, they have been reported to be closely associated with many kinds of tumors including glioma [9]. Strong evidence has shown that many miRNAs have positive or negative effects on glioma [10]. By comparing miRNA expression in different grades of glioma, studies have revealed potential miRNA functions.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-346 inhibits the growth of glioma by directly targeting NFIB

Zhang

et al. 2019

Cancer Cell Int

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BackgroundGlioma is considered one of the most common tumors and has a poor prognosis. Recently, microRNAs (miRNAs) have been reported to be strongly linked to various human tumors including glioma. In this study, we investigated a new anticancer miRNA, miR-346, to determine the effects and mechanism of miR-346 and its downstream target gene NFIB on tumors.MethodsLentivirus transfection, real-time PCR, western blotting, immunohistochemistry, cell proliferation assays, and mouse experiments were used to examine the relationship between miR-346 and its regulation of NFIB in glioma cells.ResultsThe expression of miR-346 was downregulated in glioma cells. Overexpression of miR-346 arrested the cell cycle of glioma cells and inhibited their proliferation in vitro and in vivo. NFIB was a direct target of miR-346, whose expression was reduced by the miRNA. Overexpression of NFIB reversed all tested functions of miR-346.ConclusionmiR-346 inhibited the growth of glioma cells by targeting NFIB and may be a new prognostic and diagnostic biomarker for glioma.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-346 inhibits the growth of glioma by directly targeting NFIB

Zhang

et al. 2019

Cancer Cell Int

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“…At 24 h following incubation, only ≈20% of the TMZ was detected in the medium in the former case (M 0 Mφ), whereas about 85% of the TMZ was detected in the latter case (M 1 Mφ). Relative to normal tissue environments, tumor tissue environments are highly reductive with at least fourfold higher concentrations of GSH, [30] which can effectively cleave the disulfide bonds within the prodrug NPs, releasing TMZ. These experimental data suggest that the prodrug/drug release from the Mφ-hitchhiked NPs is limited before they arrive at the tumor site, avoiding systemic cytotoxicity, while efficient prodrug/drug release occurs upon their arrival.…”

Section: Resultsmentioning

confidence: 99%

A Noninvasive Gut‐to‐Brain Oral Drug Delivery System for Treating Brain Tumors

Miao

Chen

et al. 2021

Advanced Materials

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head shaving, general anesthesia, installation of multielement extracranial systems, and others) that are needed for focused ultrasound treatments and their potential adverse thermal/mechanical effects on healthy tissues limit their clinical use. [3] Oral chemotherapy has the advantages of avoiding the pain and contamination that are frequently caused by injections and allows patients to take their drugs at home, favoring their quality of life. Unfortunately, most orally administered anticancer therapeutics fail to reach the intracerebral pathological regions because of two major biological barriers, the intestinal epithelial barrier (IEB) and the BBB, which are located between the gut and the brain. The IEB is an important physical barrier against pathogens and toxins in the digestive tract, whereas the BBB protects the brain from harmful substances in the bloodstream. [4] These two biological barriers together markedly limit the accumulation of therapeutic molecules at the brain tumor site when a drug is administered via the oral route, posing a great challenge to the use of conventional medications.Most orally administered drugs fail to reach the intracerebral regions because of the intestinal epithelial barrier (IEB) and the blood-brain barrier (BBB), which are located between the gut and the brain. Herein, an oral prodrug delivery system that can overcome both the IEB and the BBB noninvasively is developed for treating gliomas. The prodrug is prepared by conjugating an anticancer drug on β-glucans using a disulfide-containing linker. Following oral administration in glioma-bearing mice, the as-prepared prodrug can specifically target intestinal M cells, transpass the IEB, and be phagocytosed/ hitchhiked by local macrophages (Mφ). The Mφ-hitchhiked prodrug is transported to the circulatory system via the lymphatic system, crossing the BBB. The tumor-overexpressed glutathione then cleaves the disulfide bond within the prodrug, releasing the active drug, improving its therapeutic efficacy. These findings reveal that the developed prodrug may serve as a gut-to-brain oral drug delivery platform for the well-targeted treatment of gliomas.

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“…Through the progress in DNA nanotechnology, nano‐level machines/devices have been designed with excellent performance combined with the biological compatibility of DNA, suitable for biomedical applications 82–85 . DNA nanotechnology has become an evolutionary approach for targeting biomolecules in vitro as well as systemically 86–88 . These materials have been investigated for exhibiting improved treatment efficacy and safety profile compared to the prospects of current diagnostic/treatment options 89–91 .…”

Section: Summary and Outlooksmentioning

confidence: 99%

Development and functionalization of DNA nanostructures for biomedical applications

Zou

Neelakantan

Zhang

2021

J Chinese Chemical Soc

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Nanomaterials are excellent drug delivery systems, yet, they must be functionalized in a manner compatible with the biological environment. Regarding delivery of the payloads, it is critical to monitor the nanocarrier's biocompatibility and the ability to control its drug encapsulation and release, as well as targeting. The current challenges include avoiding negative host immune responses, optimizing stability in biological environments, and achieving precise interactions with the targets. Contemporary advances in structural DNA nanotechnology, DNA origami, and supramolecular DNA assembly make it possible to produce complex multi‐functional DNA nanostructures, wherein precise control of the size, geometry, and appearance of the ligands is feasible. DNA nanostructures offer ease of synthesis and conjugation of functional moieties to target the release of cargo or to analyze important biomarkers for diagnostics. Furthermore, the biocompatibility, programmability, responsiveness to biomolecules, cell‐surfaces, and organisms make such DNA nanomaterials highly suitable for potential translational applications. This overview summarizes the recent developments in functionalizing, stabilizing, and applying DNA nanostructures for potential biomedical applications.

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A GSH‐Gated DNA Nanodevice for Tumor‐Specific Signal Amplification of microRNA and MR Imaging–Guided Theranostics

Cited by 64 publications

References 59 publications

MicroRNA-346 inhibits the growth of glioma by directly targeting NFIB

MicroRNA-346 inhibits the growth of glioma by directly targeting NFIB

A Noninvasive Gut‐to‐Brain Oral Drug Delivery System for Treating Brain Tumors

Development and functionalization of DNA nanostructures for biomedical applications

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