Current Transport Systems and Clinical Applications for Small Interfering RNA (siRNA) Drugs

Liu, Fang; Wang, Chunfang; Gao, Yuantao; Li, Xiao; Tian, Feng; Zhang, Yongtao; Fu, Mingyang; Li, Pengfei; Wang, Yali; Wang, Fei

doi:10.1007/s40291-018-0338-8

Cited by 30 publications

(21 citation statements)

References 215 publications

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“…Those novel findings provided a potential therapeutic target in HNC. However, delivery of siRNA into cancer cells in vivo remained a major barrier due to the limiting characteristics of siRNA, including its polyanionic charge, low cell membrane permeability and low stability in the presence of serum nucleases (30,31). A number of siRNA delivery vehicles, including nonreplicating viruses, oncolytic virus platforms, adenovirus and proteins, have been widely investigated in order to address these challenges (32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

“…A number of siRNA delivery vehicles, including nonreplicating viruses, oncolytic virus platforms, adenovirus and proteins, have been widely investigated in order to address these challenges (32)(33)(34)(35). Although a number of creative vectors have given promising results, their safety, biocompatibility and low transduction efficiency are notable concerns for the delivery of siRNA (30,31). Exosomes, produced endogenously from endosomes by numerous types of cells, are able to fuse with cancer cell membranes naturally, with promising safety, biocompatibility and transduction efficiency (30,36).…”

Section: Discussionmentioning

confidence: 99%

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Exosome‑delivered TRPP2 siRNA inhibits the epithelial‑mesenchymal transition of FaDu cells

et al. 2018

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The prognosis for patients with head and neck cancer (HNC) remains poor, owing to uncontrolled tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) serves an important role in this invasion and metastasis, and transient receptor potential polycystic 2 (TRPP2) enhances metastasis and invasion by regulating EMT in human laryngeal squamous cell carcinoma. The present study examined whether exosomes/TRPP2 small interfering RNA (siRNA) complexes were able to reduce EMT by suppressing TRPP2 expression in FaDu cells, a cell line of human pharyngeal squamous cell carcinoma. Using agarose gel electrophoresis, it was determined that exosome/TRPP2 siRNA complexes were stable in the presence of nucleases and serum. A fluorescence assay and western blotting analysis was performed, and it was reported that the FaDu cells took up exosomes, the exosomes effectively delivered TRPP2 siRNA into FaDu cells and that exosome/TRPP2 siRNA complexes significantly suppressed TRPP2 protein expression levels in FaDu cells. Furthermore, expression levels of E-cadherin were significantly increased, whereas expression levels of N-cadherin and vimentin were significantly decreased in FaDu cells transfected with TRPP2 siRNA. Thus, exosome/TRPP2 siRNA complexes markedly suppressed TRPP2 expression and EMT in FaDu cells. These results suggested that further development of exosome/TRPP2 siRNA complexes for use as an RNA-based gene therapy in the treatment of HNC is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exosome‑delivered TRPP2 siRNA inhibits the epithelial‑mesenchymal transition of FaDu cells

et al. 2018

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“…Specifically, the discovery of interference RNA (RNAi) and the development of siRNA molecules have allowed the possibility of controlling a specific and unique mechanism of action in the regulation of genes [ 3 , 4 ]. This has been translated into better results in terms of selectivity and efficiency compared to other therapeutic agents used in gene therapy, such as pDNA and oligonucleotides [ 5 , 6 ]. The siRNA molecules can block specific regions in the messenger RNA (mRNA) sequence through the formation of a RNA-induced silencing complex (RISC), thus suppressing the synthesis of the target pathogenic protein.…”

Section: Introductionmentioning

confidence: 99%

Protein Expression Knockdown in Cancer Cells Induced by a Gemini Cationic Lipid Nanovector with Histidine-Based Polar Heads

et al. 2020

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A histidine-based gemini cationic lipid, which had already demonstrated its efficiency as a plasmid DNA (pDNA) nanocarrier, has been used in this work to transfect a small interfering RNA (siRNA) into cancer cells. In combination with the helper lipid monoolein glycerol (MOG), the cationic lipid was used as an antiGFP-siRNA nanovector in a multidisciplinary study. Initially, a biophysical characterization by zeta potential (ζ) and agarose gel electrophoresis experiments was performed to determine the lipid effective charge and confirm siRNA compaction. The lipoplexes formed were arranged in Lα lamellar lyotropic liquid crystal phases with a cluster-type morphology, as cryo-transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS) studies revealed. Additionally, in vitro experiments confirmed the high gene knockdown efficiency of the lipid-based nanovehicle as detected by flow cytometry (FC) and epifluorescence microscopy, even better than that of Lipofectamine2000*, the transfecting reagent commonly used as a positive control. Cytotoxicity assays indicated that the nanovector is non-toxic to cells. Finally, using nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS), apolipoprotein A-I and A-II followed by serum albumin were identified as the proteins with higher affinity for the surface of the lipoplexes. This fact could be beyond the remarkable silencing activity of the histidine-based lipid nanocarrier herein presented.

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“…The density of the siRNA molecules on the AuNP surface is an indicator of the efficiency of the nucleic acid transporter: the higher the density, the less amount of the preparation can be administered, thus reducing the toxic effect of siRNA [24].…”

Section: Resultsmentioning

confidence: 99%

Long-term stability and scale-up of noncovalently bound gold nanoparticle-siRNA suspensions

Epanchintseva

Poletaeva

Pyshnyi

et al. 2019

Beilstein J. Nanotechnol.

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Gold nanoparticles (AuNPs) are a platform for the creation of nanoconstructions that can have a variety of functions, including the delivery of therapeutic nucleic acids. We previously designed a AuNP/small interfering RNA (siRNA) nanoconstruction consisting of siRNA noncovalently bound on the AuNP surface and showed that this construction, when coated with a lipid shell, was an efficient vehicle for the delivery of siRNA into cells. The goal of the present work was to study the possibility of scaling up the synthesis of AuNP-siRNA and its long-term storage without loss of physicochemical characteristics and siRNA duplex integrity as well as siRNA surface density. Dynamic light scattering, transmission electron microscopy, UV–vis spectroscopy, and electrophoresis were used to study the effect of scaling up the AuNP-siRNA synthesis and long term storage of its suspension on physicochemical properties of the samples and integrity of the siRNA duplex. It was shown that a ten-fold increase in the volume of the reaction mixture decreased the surface density of siRNA by about 10%, which influenced the corresponding physicochemical characteristics of the AuNP-siRNA suspension. The storage of the AuNP-siRNA suspension at 4 °C for different times resulted in the formation of particle clusters of high colloidal stability as demonstrated by conventional methods. These clusters completely disintegrated when albumin was added, indicating that they are agglomerates (and not aggregates) of AuNP-siRNA. The AuNPs-siRNA nanoconstruction demonstrated integrity of the siRNA duplex and high stability of the siRNA surface density during storage for seven months at 4 °C. Thus, it can be concluded that it is possible to scale-up the synthesis of noncovalent AuNP-siRNA and to obtain a nanoconstruction possessing high stability in terms of physicochemical characteristics and siRNA surface density for a long period.

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Current Transport Systems and Clinical Applications for Small Interfering RNA (siRNA) Drugs

Cited by 30 publications

References 215 publications

Exosome‑delivered TRPP2 siRNA inhibits the epithelial‑mesenchymal transition of FaDu cells

Exosome‑delivered TRPP2 siRNA inhibits the epithelial‑mesenchymal transition of FaDu cells

Protein Expression Knockdown in Cancer Cells Induced by a Gemini Cationic Lipid Nanovector with Histidine-Based Polar Heads

Long-term stability and scale-up of noncovalently bound gold nanoparticle-siRNA suspensions

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