Synthesis and characterization of Fe3O4-PEG-LAC-chitosan-PEI nanoparticle as a survivin siRNA delivery system

2016 ◽  
Vol 36 (3) ◽  
pp. 227-237 ◽  
Author(s):  
S Arami ◽  
MR Rashidi ◽  
M Mahdavi ◽  
M Fathi ◽  
AA Entezami

The limited effectiveness of the conventional methods for cancer treatment makes the researchers to find novel safe and effective therapeutic strategies. One of these strategies is to use small interfering RNAs (siRNAs). A major challenge here is the siRNA delivery into the cells. The purpose of this study was to design and prepare a biocompatible, biodegradable, and safe nanosized particle for siRNA delivery into human breast cancer MCF-7 and leukemia K562 cells. Chemically synthesized magnetic nanoparticles containing polyethyleneglycol-lactate polymer (PEG-LAC), chitosan, and polyethyleneimine (PEI) were successfully prepared and used as a gene delivery vehicle. The nanoparticles were characterized by Fourier transform infrared spectroscopy and zeta potential. The Fe3O4-PEG-LAC-chitosan-PEI nanoparticle showed efficient and stable survivin siRNA loading in gel retardation assay. The cytotoxicity of the prepared nanoparticle was studied using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and was compared with that of mitoxantrone (MTX) in combination with the prepared siRNA delivery system to evaluate the possible synergic effect of MTX and survivin siRNA. The nanoparticles with and without noncomplementary siRNA showed low toxicity against both cell lines; however, a twofold decrease was observed in cell survival percent after MTX addition to MCF-7 cells treated with either nanoparticle itself or complexed with noncomplementary siRNA. While survivin siRNA nanoplex caused threefold decrease in the cell survival percent, its combination with MTX did not result in a significant increase in the cytotoxic effect. Therefore, Fe3O4-PEG-LAC-chitosan-PEI nanoparticle should be considered as a potential carrier for enhanced survivin siRNA delivery into MCF-7 and K562 cells.

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.


2018 ◽  
Vol 24 (16) ◽  
pp. 1788-1800 ◽  
Author(s):  
Kye-Soo Cho ◽  
Seo-Jin Hong ◽  
Min-Hye Ahn ◽  
Sukdeb Pal ◽  
Pill-Hoon Choung ◽  
...  

Background: Cancer poses a major public health issue, is linked with high mortality rates across the world, and shows a strong interplay between genetic and environmental factors. To date, common therapeutics, including chemotherapy, immunotherapy, and radiotherapy, have made significant contributions to cancer treatment, although diverse obstacles for achieving the permanent “magic bullet” cure have remained. Recently, various anticancer therapeutic agents designed to overcome the limitations of these conventional cancer treatments have received considerable attention. One of these promising and novel agents is the siRNA delivery system; however, poor cellular uptake and altered siRNA stability in physiological environments have limited its use in clinical trials. Therefore, developing the ideal siRNA delivery system with low cytotoxicity, improved siRNA stability in the body’s circulation, and prevention of its rapid clearance from bodily fluids, is rapidly emerging as an innovative therapeutic strategy to combat cancer. Moreover, active targeting using ligand moieties which bind to over-expressed receptors on the surface of cancer cells would enhance the therapeutic efficiency of siRNA. Conclusion: In this review, we provide 1) an overview of the non-viral carrier associated with siRNA delivery for cancer treatment, and 2) a description of the five major cancer-targeting ligands.


Author(s):  
Jiehua Zhou ◽  
Haitang Li ◽  
Shirley Li ◽  
John Zaia ◽  
John Rossi

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.


2019 ◽  
Vol 57 (2) ◽  
pp. 635-649 ◽  
Author(s):  
J. H. Azambuja ◽  
R. S. Schuh ◽  
L. R. Michels ◽  
N. E. Gelsleichter ◽  
L. R. Beckenkamp ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alicia Gamboa ◽  
Selina F. Urfano ◽  
Katrina Hernandez ◽  
Deborah A. Fraser ◽  
Luladey Ayalew ◽  
...  

AbstractThe higher-order architecture observed in biological systems, like viruses, is very effective in nucleic acid transport. The replications of this system has been attempted with both synthetic and naturally occurring polymers with mixed results. Here we describe a peptide/siRNA quaternary complex that functions as an siRNA delivery system. The rational design of a peptide assembly is inspired by the viral capsids, but not derived from them. We selected the collagen peptide (COL) to provide the structural stability and the folding framework, and hybridize it with the cell penetrating peptide (CPP) that allows for effective penetration of biological barriers. The peptide/siRNA quaternary complex forms stoichiometric, 10 nm nanoparticles, that show fast cellular uptake (<30 min), effective siRNA release, and gene silencing. The complex provides capsid-like protection for siRNA against nucleases without being immunostimulatory, or cytotoxic. Our data suggests that delivery vehicles based on synthetic quaternary structures that exhibit higher-order architecture may be effective in improving delivery and release of nucleic acid cargo.


2017 ◽  
Vol 7 (4) ◽  
pp. 507-515 ◽  
Author(s):  
Baoling Chen ◽  
Kimoon Yoo ◽  
Wen Xu ◽  
Ran Pan ◽  
Xiao Xia Han ◽  
...  

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