scholarly journals Endogenous microRNA triggered enzyme-free DNA logic self-assembly for amplified bioimaging and enhanced gene therapy via in situ generation of siRNAs

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qinghua Jiang ◽  
Shuzhen Yue ◽  
Kaixin Yu ◽  
Tian Tian ◽  
Jian Zhang ◽  
...  

Abstract Background Small interfering RNA (siRNA) has emerged as a kind of promising therapeutic agents for cancer therapy. However, the off-target effect and degradation are the main challenges for siRNAs delivery. Herein, an enzyme-free DNA amplification strategy initiated by a specific endogenous microRNA has been developed for in situ generation of siRNAs with enhanced gene therapy effect on cervical carcinoma. Methods This strategy contains three DNA hairpins (H1, H2/PS and H3) which can be triggered by microRNA-21 (miR-21) for self-assembly of DNA nanowheels (DNWs). Notably, this system is consistent with the operation of a DNA logic circuitry containing cascaded “AND” gates with feedback mechanism. Accordingly, a versatile biosensing and bioimaging platform is fabricated for sensitive and specific analysis of miR-21 in HeLa cells via fluorescence resonance energy transfer (FRET). Meanwhile, since the vascular endothelial growth factor (VEGF) antisense and sense sequences are encoded in hairpin reactants, the performance of this DNA circuit leads to in situ assembly of VEGF siRNAs in DNWs, which can be specifically recognized and cleaved by Dicer for gene therapy of cervical carcinoma. Results The proposed isothermal amplification approach exhibits high sensitivity for miR-21 with a detection limit of 0.25 pM and indicates excellent specificity to discriminate target miR-21 from the single-base mismatched sequence. Furthermore, this strategy achieves accurate and sensitive imaging analysis of the expression and distribution of miR-21 in different living cells. To note, compared to naked siRNAs alone, in situ siRNA generation shows a significantly enhanced gene silencing and anti-tumor effect due to the high reaction efficiency of DNA circuit and improved delivery stability of siRNAs. Conclusions The endogenous miRNA-activated DNA circuit provides an exciting opportunity to construct a general nanoplatform for precise cancer diagnosis and efficient gene therapy, which has an important significance in clinical translation. Graphic abstract

2021 ◽  
Author(s):  
Qinghua Jiang ◽  
Shuzhen Yue ◽  
Kaixin Yu ◽  
Tian Tian ◽  
Jian Zhang ◽  
...  

Abstract BackgroundSmall interfering RNA (siRNA) has emerged as a kind of promising therapeutic agents for cancer therapy. However, the off-target effect and degradation are the main challenges for siRNAs delivery. Herein, an enzyme-free DNA amplification strategy initiated by a specific endogenous microRNA has been developed for in situ generation of siRNAs with enhanced gene therapy effect on cervical carcinoma.MethodsThis strategy contains three DNA hairpins (H1, H2/PS and H3) which can be triggered by microRNA-21 (miR-21) for self-assembly of DNA nanowheels (DNWs). Notably, this system is consistent with the operation of a DNA logic circuitry containing cascaded “AND” gates with feedback mechanism. Accordingly, a versatile biosensing and bioimaging platform is fabricated for sensitive and specific analysis of miR-21 in HeLa cells via fluorescence resonance energy transfer (FRET). Meanwhile, since the vascular endothelial growth factor (VEGF) antisense and sense sequences are encoded in hairpin reactants, the performance of this DNA circuit leads to in situ assembly of VEGF siRNAs in DNWs, which can be specifically recognized and cleaved by Dicer for gene therapy of cervical carcinoma. ResultsThe proposed isothermal amplification approach exhibits high sensitivity for miR-21 with a detection limit of 0.25 pM and indicates excellent specificity to discriminate target miR-21 from the single-base mismatched sequence. Furthermore, this strategy achieves accurate and sensitive imaging analysis of the expression and distribution of miR-21 in different living cells. To note, compared to naked siRNAs alone, in situ siRNA generation shows a significantly enhanced gene silencing and anti-tumor effect due to the high reaction efficiency of DNA circuit and improved delivery stability of siRNAs.ConclusionThe endogenous miRNA-activated DNA circuit provides an exciting opportunity to construct a general nanoplatform for precise cancer diagnosis and efficient gene therapy, which has an important significance in clinical translation.


2019 ◽  
Vol 10 (6) ◽  
pp. 1651-1658 ◽  
Author(s):  
Shuzhen Yue ◽  
Xinyue Song ◽  
Weiling Song ◽  
Sai Bi

Branched catalytic hairpin assembly is proposed for dynamic self-assembly of DNA dendrimers for signal amplification and in situ imaging of microRNAs in live cells with high sensitivity and selectivity.


2016 ◽  
Vol 88 (12) ◽  
pp. 6418-6424 ◽  
Author(s):  
Shuxia Xu ◽  
Xianming Li ◽  
Chaobi Li ◽  
Jialin Li ◽  
Xinfeng Zhang ◽  
...  

RSC Advances ◽  
2014 ◽  
Vol 4 (95) ◽  
pp. 53327-53334 ◽  
Author(s):  
Braja Gopal Bag ◽  
Rakhi Majumdar

Formation of vesicular gel and gel–gold nanoparticle hybrid material from arjunolic acid extractable from the saw-dust of Terminalia arjuna.


2010 ◽  
Vol 20 (36) ◽  
pp. 7715 ◽  
Author(s):  
Jong Won Chung ◽  
Byeong-Kwan An ◽  
Fumio Hirato ◽  
Jong H. Kim ◽  
Hiroshi Jinnai ◽  
...  

Nanoscale ◽  
2018 ◽  
Vol 10 (39) ◽  
pp. 18555-18564
Author(s):  
Daragh Byrne ◽  
Colette McDonagh

Plasmonic cavities are grown in situ via Au labelled antibodies yielding a highly responsive fluorescence based biosensing platform.


Polymers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1643 ◽  
Author(s):  
Yue-liang Zhai ◽  
Qiu-bo Wang ◽  
Hao Yu ◽  
Xiao-yuan Ji ◽  
Xian Zhang

The calcium ion (Ca2+) isa highly versatile intracellular signal messenger regulating many different cellular functions. It is important to design probes with good fluorescence and two-photon (TP) active cross-sections (Φδ) to explore the concentration distribution of Ca2+. In this manuscript, a novel TP fluorescence calcium probe (BAPTAVP) with positive charges, based on the classical Ca2+ indicator of BAPTA (1,2-bis(2-aminophenoxy)-ethane-N,N,N’,N’-tetra acetic acid), and a conjugated polymer (PCBMB) with negative charges were designed and synthesized. The results from transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and the zeta potential (ZP) showed that nanoparticles were obtained by the self-assembly of PCBMB and BAPTAVP. Moreover, the fluorescence properties of BAPTAVP were effectively improved by fluorescence resonance energy transfer (FRET) with PCBMB and attenuating the intramolecular charge transfer (ICT) after the addition of Ca2+. The quantum yield and Φδ of PCBMB-BAPTAVP increased by about four and six times in comparison to those of BAPTAVP, respectively. The TP fluorescence imaging experiments indicated that the PCBMB-BAPTAVP system could effectively detect Ca2+ in living cells with high sensitivity.


Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.


Author(s):  
Kazumasa Funabiki ◽  
Toshiya Gotoh ◽  
Ryunosuke Kani ◽  
Toshiyasu Inuzuka ◽  
Yasuhiro Kubota

A highly diastereo- and enantioselective organocatalytic method to synthesise erythritols bearing a trifluoromethyl group has been investigated.


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