Preparation of siRNA encapsulated nanoliposomes suitable for siRNA delivery by simply discontinuous mixing

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Title
Preparation of siRNA encapsulated nanoliposomes suitable for siRNA delivery by simply discontinuous mixing
Author(s)
A A Mokhtarieh; Jieun Lee; Semi Kim; Myung Kyu Lee
Bibliographic Citation
Biochimica et Biophysica Acta-Biomembranes, vol. 1860, no. 6, pp. 1318-1325
Publication Year
2018
Abstract
Previously a scalable and extrusion-free method has been developed for efficient liposomal encapsulation of DNA by twice stepwise mixing of lipids in ethanol and DNA solution using T-shape mixing chamber. In this study, we prepared nanoliposomes encapsulating siRNA by simply discontinuous mixing of lipids in ethanol/ether/water mixture and acidic siRNA solution without use of special equipment. The simple mixing siRNA/liposomal particles (siRNA/SMLs) prepared using ethanol/ether/water (3:1:1) mixture showed 120.4 ± 20.2 nm particle size, 0.174 ± 0.033 polydispersity and 86.5 ± 2.76% siRNA encapsulation rate. In addition, the SMLs almost completely protected the encapsulated siRNA from RNase A digestion. Coupling of anti-human epidermal growth factor receptor (EGFR) Fab′ to siRNA/SMLs enhanced EGFR-specific cell penetration of SMLs and induced siRNA dependent gene silencing. Unexpectedly, the Cy5.5-labeled Fab′ showed almost no in vivo targeting to the xenografted A549 tumors in SCID-NOD mice. However, multiple injection of the unmodified siRNA/SMLs accumulated in the tumors and induced siRNA-dependent in vivo gene silencing. These results demonstrate that the siRNA/SMLs can be used as a siRNA delivery tool for gene therapy
Keyword
Fab′ preparation and labelingGene silencingSimple mixing nanoliposomeTarget specific deliverysiRNA encapsulation
ISSN
0005-2736
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbamem.2018.02.027
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Division of Biomaterials Research > Bionanotechnology Research Center > 1. Journal Articles
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