Tetrahedral <scp>DNA</scp> nanostructures facilitate neural stem cell migration <i>via</i> activating <scp>RHOA</scp>/<scp>ROCK</scp>2 signalling pathway

Ma, Wenjuan; Xie, Xueping; Shao, Xin; Zhang, Yuxin; Mao, Chenchen; Zhan, Yanhu; Zhao, Dan; Liu, Mengting; Li, Qianshun; Lin, Yunfeng

doi:10.1111/cpr.12503

Cited by 52 publications

(42 citation statements)

References 61 publications

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“…Thus, the combination of aptamers and DNA tetrahedrons lays the foundation for targeted drug delivery and next-generation treatments. Our results showed that the TDN could enter cells without transfection agents, which is similar to the results of Walsh et al and Ma et al [ 15 , 19 ]. Compared with that of the TDN, uptake of the Apt-TDN by U87MG cells was significantly increased.…”

Section: Discussionsupporting

confidence: 92%

“…Research has shown that ANG-TDN can cross the BBB. Ma et al [ 19 ] suggested that tetrahedral DNA nanostructures can enter neural stem cells (NSCs) without the need for transfection agents, where they promote neural stem cell migration, proliferation, and differentiatio n[ 20 ], and have great potential for neural tissue repair and regeneration. Therefore, we investigated the possibility of the use of TDN in glioma therapy and enhancing its targeting ability.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Glioma is one of the deadliest intrinsic brain tumours due to its invasive growth. The effect of glioma treatment is poor because of the presence of the blood-brain barrier and blood tumour barrier and insufficient drug targeting. DNA tetrahedrons (TDN) show great potential for drug delivery and may be a novel therapeutic strategy for glioma. In this study, we used TDN to deliver doxorubicin (DOX) for the glioma therapy. Gint4.T, an aptamer that could recognize platelet-derived growth factor receptor β on tumour cell, was used to modify TDN (Apt-TDN) for targeted drug delivery. The TDN were self-assembled by one-step synthesis, which showed small size (10 nm) and negative charge. Fetal bovine serum test showed its stability as a drug delivery vehicle. Apt-TDN could be effectively taken up by U87MG cells. Compared with DOX and DOX@TDN (TDN loaded with DOX), the DOX@Apt-TDN (Gint4.T-modified TDN loaded with DOX) showed more early apoptosis rate, higher cell cycle arrest, and greater cytotoxicity towards U87MG cells. In conclusion, our findings indicated that DOX@Apt-TDN provides a novel therapy with promising clinical application for gliomas patients.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…The specific synthesis details of tFNAs can be seen in previous research reports [ [26] , [27] , [28] ]. S1–S4 single DNA strands - Table 1 showed the sequence of bases for each strand of DNA.…”

Section: Methodsmentioning

confidence: 99%

Erythromycin loaded by tetrahedral framework nucleic acids are more antimicrobial sensitive against Escherichia coli (E. coli)

Sun

Liu

Zhang

et al. 2021

Bioactive Materials

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Erythromycin is a commonly used broad-spectrum antibiotic, but resistance to this antibiotic makes its use less effective. Considerable efforts, beside finding alternatives, are needed to enhance its antimicrobial effect and stability against bacteria. Tetrahedral framework nucleic acids (tFNAs), a novel delivery vehicle with a three-dimensional nanostructure, have been studied as a carrying platform of antineoplastic drugs. In this study, the use of tFNAs in delivering erythromycin into Escherichia coli ( E. coli ) was investigated for the first time. The tFNAs vehicle increased the bacterial uptake of erythromycin and promoted membrane destabilization. Moreover, it increased the permeability of the bacterial cell wall, and reduced drug resistance by improving the movement of the drug across the membrane. The tFNAs-based delivery system enhanced the effects of erythromycin against E. coli . It may therefore provide an effective delivery vehicle for erythromycin in targeting antibiotic-resistant bacteria with thick cell wall.

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“…To confirm the successful synthesis of As-TDN-R, 3% agarose gel was used to separate each of the DNA samples based on their migration speed. 22 As shown in Figure 1A, the first four bands represented four single-strand DNA (Lane 1: As-s1, Lane 2: si-s2, Lane 3: s3, Lane 4: s4). Due to external modification, band 1 and band 2 moved slowly compared with Scheme 1 Schematic illustration for the synthesis of As-TDN-R. Aptamer AS1411 is linked on the strand of s1 for selective delivery into the glioma cells.…”

Section: Dovepressmentioning

confidence: 99%

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

Zhou

Yang

Wang

et al. 2021

IJN

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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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Tetrahedral DNA nanostructures facilitate neural stem cell migration via activating RHOA/ROCK2 signalling pathway

Cited by 52 publications

References 61 publications

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

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

Erythromycin loaded by tetrahedral framework nucleic acids are more antimicrobial sensitive against Escherichia coli (E. coli)

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

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