scholarly journals Amylose-Based Cationic Star Polymers for siRNA Delivery

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Tomoki Nishimura ◽  
Kaori Umezaki ◽  
Sada-atsu Mukai ◽  
Shin-ichi Sawada ◽  
Kazunari Akiyoshi

A new siRNA delivery system using a cationic glyco-star polymer is described. Spermine-modified 8-arm amylose star polymer (with a degree of polymerization of approximately 60 per arm) was synthesized by chemoenzymatic methods. The cationic star polymer effectively bound to siRNA and formed spherical complexes with an average hydrodynamic diameter of 230 nm. The cationic 8-arm star polymer complexes showed superior cellular uptake characteristics and higher gene silencing effects than a cationic 1-arm polymer. These results suggest that amylose-based star polymers are a promising nanoplatform for glycobiomaterials.

2014 ◽  
Vol 50 (58) ◽  
pp. 7806-7809 ◽  
Author(s):  
Hangxiang Wang ◽  
Wei Chen ◽  
Haiyang Xie ◽  
Xuyong Wei ◽  
Shengyong Yin ◽  
...  

A practical and tumor cell-specific siRNA delivery system was developedviasingle-step self-assembly of an arginine-rich chimeric peptide with siRNA.


2014 ◽  
Vol 185 ◽  
pp. 109-120 ◽  
Author(s):  
Eliz Amar-Lewis ◽  
Aharon Azagury ◽  
Ramesh Chintakunta ◽  
Riki Goldbart ◽  
Tamar Traitel ◽  
...  

2011 ◽  
Vol 436 (2) ◽  
pp. 351-362 ◽  
Author(s):  
Gregory J. Tesz ◽  
Myriam Aouadi ◽  
Matthieu Prot ◽  
Sarah M. Nicoloro ◽  
Emilie Boutet ◽  
...  

Phagocytic macrophages and dendritic cells are desirable targets for potential RNAi (RNA interference) therapeutics because they often mediate pathogenic inflammation and autoimmune responses. We recently engineered a complex 5 component glucan-based encapsulation system for siRNA (small interfering RNA) delivery to phagocytes. In experiments designed to simplify this original formulation, we discovered that the amphipathic peptide Endo-Porter forms stable nanocomplexes with siRNA that can mediate potent gene silencing in multiple cell types. In order to restrict such gene silencing to phagocytes, a method was developed to entrap siRNA–Endo-Porter complexes in glucan shells of 2–4 μm diameter in the absence of other components. The resulting glucan particles containing fluorescently labelled siRNA were readily internalized by macrophages, but not other cell types, and released the labelled siRNA into the macrophage cytoplasm. Intraperitoneal administration of such glucan particles containing siRNA–Endo-Porter complexes to mice caused gene silencing specifically in macrophages that internalized the particles. These results from the present study indicate that specific targeting to phagocytes is mediated by the glucan, whereas Endo-Porter peptide serves both to anchor siRNA within glucan particles and to catalyse escape of siRNA from phagosomes. Thus we have developed a simplified siRNA delivery system that effectively and specifically targets phagocytes in culture or in intact mice.


2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Jiangyu Wu ◽  
Weizhe Huang ◽  
Ziying He

RNA interference (RNAi) was first literaturally reported in 1998 and has become rapidly a promising tool for therapeutic applications in gene therapy. In a typical RNAi process, small interfering RNAs (siRNA) are used to specifically downregulate the expression of the targeted gene, known as the term “gene silencing.” One key point for successful gene silencing is to employ a safe and efficient siRNA delivery system. In this context, dendrimers are emerging as potential nonviral vectors to deliver siRNA for RNAi purpose. Dendrimers have attracted intense interest since their emanating research in the 1980s and are extensively studied as efficient DNA delivery vectors in gene transfer applications, due to their unique features based on the well-defined and multivalent structures. Knowing that DNA and RNA possess a similar structure in terms of nucleic acid framework and the electronegative nature, one can also use the excellent DNA delivery properties of dendrimers to develop effective siRNA delivery systems. In this review, the development of dendrimer-based siRNA delivery vectors is summarized, focusing on the vector features (siRNA delivery efficiency, cytotoxicity, etc.) of different types of dendrimers and the related investigations on structure-activity relationship to promote safe and efficient siRNA delivery system.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yeong Chae Ryu ◽  
Kyung Ah Kim ◽  
Byoung Choul Kim ◽  
Hui-Min David Wang ◽  
Byeong Hee Hwang

Abstract Background Gene silencing using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine. Results Among the novel fusion peptides and siRNAs, nanocomplexes have enhanced cellular uptake and gene silencing effect in vitro and improved retention and gene silencing effects of siRNAs in vivo. Oligoarginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased retention time of siRNAs at the site of the tumor. Finally, nanocomplexes demonstrated significant in vivo gene silencing effect without overt tissue damage and immune cell infiltration. Conclusions The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene silencing.


2019 ◽  
Vol 819 ◽  
pp. 169-174
Author(s):  
Supusson Pengnam ◽  
Praneet Opanasopit ◽  
Theerasak Rojanarata ◽  
Nattisa Ni-yomtham ◽  
Boon Ek Yingyongnarongkul ◽  
...  

Niosomes are a lipid nanoparticle which have been widely used as non-viral carrier for therapeutic DNA or siRNA. They are formulated from non-ionic surfactant and other helper lipids. The aim of this study were to formulate niosome containing spermine-based cationic lipid with different linkers and to evaluate the efficiency of siRNA delivery in cervical cancer cell (HeLa cell). The niosomes were formulated from cholesterol (Chol), Span 20 and different cationic lipid (Ay, By, Cy and Dy) at various molar ratios. The properties of niosomes and ability of niosome to complex with siRNA were characterized. The cellular uptake, gene silencing efficiency and cytotoxicity were also determined. From the results, niosomes formulated at Chol:Span20:lipid molar ratio of 2.5:2.5:2 showed positive zeta potential and they were in nanosize (<200 nm). The binding ability of cationic niosomes to siRNA depended on types of cationic lipid. Among niosome/siRNA complexes, the niosome By/siRNA complex provided the highest gene silencing efficiency at weight ratio of 20. The highest cellular uptake also obtained by using niosome By as a carrier. The cytotoxicity revealed that cationic niosomes had low toxicity (cell viability > 80%). In conclusion, the cationic niosomes prepared from Chol, Span 20 and spermine-based cationic lipids are able to complex with siRNA and suitable for siRNA delivery with low toxicity.


2016 ◽  
Vol 17 (11) ◽  
pp. 3532-3546 ◽  
Author(s):  
Megan Dearnley ◽  
Nicholas P. Reynolds ◽  
Peter Cass ◽  
Xiaohu Wei ◽  
Shuning Shi ◽  
...  

2010 ◽  
Vol 28 (5) ◽  
pp. 1013-1022 ◽  
Author(s):  
Pieter Vader ◽  
Leonardus J. van der Aa ◽  
Johan F. J. Engbersen ◽  
Gert Storm ◽  
Raymond M. Schiffelers

2017 ◽  
Vol 8 (4) ◽  
pp. 2816-2822 ◽  
Author(s):  
Na Li ◽  
Huijun Yang ◽  
Zhengze Yu ◽  
Yanli Li ◽  
Wei Pan ◽  
...  

A nuclear-targeted siRNA delivery system was developed for long-term gene silencing in cancer cells. The nanocarrier consists of gold nanoparticles, synthetic siRNAs and nuclear localization signal peptides.


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