scholarly journals Gold-DNA nanosunflowers for efficient gene silencing with controllable transformation

2019 ◽  
Vol 5 (10) ◽  
pp. eaaw6264 ◽  
Author(s):  
Shuaidong Huo ◽  
Ningqiang Gong ◽  
Ying Jiang ◽  
Fei Chen ◽  
Hongbo Guo ◽  
...  

The development of an efficient delivery system for enhanced and controlled gene interference–based therapeutics is still facing great challenges. Fortunately, the flourishing field of nanotechnology provides more effective strategies for nucleic acid delivery. Here, the triplex-forming oligonucleotide sequence and its complementary strand were used to mediate self-assembly of ultrasmall gold nanoparticles. The obtained sunflower-like nanostructures exhibited strong near-infrared (NIR) absorption and photothermal conversion ability. Upon NIR irradiation, the large-sized nanostructure could disassemble and generate ultrasmall nanoparticles modified with c-myc oncogene silencing sequence, which could directly target the cell nucleus. Moreover, the controlled gene silencing effect could be realized by synergistically controlling the preincubation time with the self-assembled nanostructure (in vitro and in vivo) and NIR irradiation time point. This study provides a new approach for constructing more efficient and tailorable nanocarriers for gene interference applications.

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiang Li ◽  
Zhen Wang ◽  
Mian Ma ◽  
Zhouqing Chen ◽  
Xiang-long Tang ◽  
...  

Background and Purpose. Although chemodynamic therapy (CDT) is promising for cancer treatment, its clinical application is still limited because of unresolved issues. In this study, an efficient CDT agent for synergistic chemo/CDT therapy mediated by the photothermal effect was developed by an iron oxide self-assembly method. Methods. Superparamagnetic iron oxide nanoclusters (SPIOCs) were located within the core, which resulted in high photothermal conversion and outstanding generation of reactive oxygen species (ROS). The shell consisted of a human serum albumin- (HSA-) paclitaxel (PTX) layer, which extended the blood circulation time and ensured the effectiveness of the chemotherapy. Arg-Gly-Asp peptides (RGD) were linked to the naked cysteine moieties in HSA to promote the specific targeting of human glioma U87 cells by αvβ3 integrins. Continuous near-infrared light irradiation triggered and promoted the synergistic chemo/CDT therapy through the photothermal effect. Results. Our SPIOCs@HSA-RGD nanoplatform showed well biocompatibility and could target glioma specifically. Photothermal conversion and ROS burst were detected after continuous 808 nm light irradiation, and a significant antitumor effect was achieved. Conclusion. Experimental in vitro and in vivo evaluations showed that our photothermal-mediated chemo/CDT therapy could efficiently inhibit tumor growth and is therefore promising for cancer therapy.


2018 ◽  
Vol 9 (15) ◽  
pp. 3820-3827 ◽  
Author(s):  
Soonsil Hyun ◽  
Yoonhwa Choi ◽  
Ha Neul Lee ◽  
Changki Lee ◽  
Donghoon Oh ◽  
...  

A hydrocarbon stapled peptide, LKH-stEK, promotes delivery of nanomolar siRNAs leading to efficient gene silencing in mouse skin.


2020 ◽  
Vol 117 (5) ◽  
pp. 2395-2405 ◽  
Author(s):  
Xiaohong Chen ◽  
Yuxuan Chen ◽  
Huhu Xin ◽  
Tao Wan ◽  
Yuan Ping

We herein report an optogenetically activatable CRISPR-Cas9 nanosystem for programmable genome editing in the second near-infrared (NIR-II) optical window. The nanosystem, termed nanoCRISPR, is composed of a cationic polymer-coated Au nanorod (APC) and Cas9 plasmid driven by a heat-inducible promoter. The APC not only serves as a carrier for intracellular plasmid delivery but also can harvest external NIR-II photonic energy and convert it into local heat to induce the gene expression of the Cas9 endonuclease. Due to high transfection activity, the APC shows strong ability to induce a significant level of disruption in different genomic loci upon optogenetic activation. Moreover, the precise control of genome-editing activity can be simply programmed by finely tuning exposure time and irradiation time in vitro and in vivo and also enables editing at multiple time points, thus proving the sensitivity and inducibility of such an editing modality. The NIR-II optical feature of nanoCRISPR enables therapeutic genome editing at deep tissue, by which treatment of deep tumor and rescue of fulminant hepatic failure are demonstrated as proof-of-concept therapeutic examples. Importantly, this modality of optogenetic genome editing can significantly minimize the off-target effect of CRISPR-Cas9 in most potential off-target sites. The optogenetically activatable CRISPR-Cas9 nanosystem we have developed offers a useful tool to expand the current applications of CRISPR-Cas9, and also defines a programmable genome-editing strategy toward high precision and spatial specificity.


2014 ◽  
Vol 2 (32) ◽  
pp. 5302-5308 ◽  
Author(s):  
Hao Wu ◽  
Haidong Zhao ◽  
Xiaojie Song ◽  
Shen Li ◽  
Xiaojun Ma ◽  
...  

Self-assembly-induced near-infrared fluorescent nanoprobes exhibiting spontaneous lattices were prepared and evaluated for in vitro and in vivo tumor molecular imaging.


2008 ◽  
Vol 8 (5) ◽  
pp. 2187-2204 ◽  
Author(s):  
J. N. Moreira ◽  
A. Santos ◽  
V. Moura ◽  
M. C. Pedroso de Lima ◽  
S. Simões

New molecular biology techniques have uncovered the hidden role of genes in cancer. Identification of activated oncogenes, as fundamental genetic differences relative to normal cells, has made it possible to consider such genes as targets for antitumor therapy, namely by applying gene silencing strategies. In this regard, antisense oligonucleotides or small interfering RNAs, constitute promising therapeutic tools. The widespread clinical application of such molecules as modulators of gene expression, is still dependent on several aspects that limit their bioavailability, including: enhanced biological stability, favourable pharmacokinetics, enhanced tumor cell uptake and, consequently, efficient targeted delivery. One of the most promising strategies to overcome the barriers faced by gene silencing molecules, upon systemic administration, involves the use of lipid-based nanoparticles. The first part of this review aims at providing the reader with the molecular mechanism of action of the most important gene silencing molecules used in anticancer therapy. The primary obstacle for translating gene silencing technology from an effective research tool into a feasible therapeutic strategy remains its efficient delivery to the targeted cell type in vivo. Therefore, an overview of different lipid-based strategies for nucleic acid delivery will be presented on the second part. As we learn more about the pharmacokinetics and pharmacodynamics of the carrier and/or of the gene silencing molecules, it will be possible to further improve the delivery strategy that likely in the future will lead to the ideal non-viral particle for targeted cancer systemic gene silencing.


Nano Research ◽  
2016 ◽  
Vol 10 (2) ◽  
pp. 503-519 ◽  
Author(s):  
Seongchan Kim ◽  
Yuri Choi ◽  
Ginam Park ◽  
Cheolhee Won ◽  
Young-Joon Park ◽  
...  

Small ◽  
2016 ◽  
Vol 12 (27) ◽  
pp. 3604-3604 ◽  
Author(s):  
Chao Chen ◽  
Paola Posocco ◽  
Xiaoxuan Liu ◽  
Qiang Cheng ◽  
Erik Laurini ◽  
...  

Small ◽  
2016 ◽  
Vol 12 (27) ◽  
pp. 3667-3676 ◽  
Author(s):  
Chao Chen ◽  
Paola Posocco ◽  
Xiaoxuan Liu ◽  
Qiang Cheng ◽  
Erik Laurini ◽  
...  

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.


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