Journal
BIOMATERIALS
Volume 34, Issue 4, Pages 1337-1343Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.10.043
Keywords
Drug release; Peptide; Nanoparticle; Liposome
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Education, Culture, Sports, Science and Technology of Japanese government
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Emerging evidence indicates that the efficiency of siRNA loading into an RNA-induced silencing complex (RISC) is a major factor in gene silencing at low doses. In particular, the release of siRNA from components delivered to the cytoplasm could be a first step for achieving maximum gene knockdown effect in siRNA delivery vector. To test this hypothesis, we used a stearylated-octahistidine (STR-H8) as a pH responsive polycation that facilitates the efficient release of siRNA into the cytoplasm, while a stearylated-octaarginine (STR-R8) was used as a conventional cationic polycation. As a fundamental structure, we used octaarginine (R8) and GALA, as a pH-sensitive fusogenic peptide, modified lipid envelope-type nanoparticles (R8/GAIA-MENDSUV), as reported previously. When STR-H8/siRNA condensed complexes were loaded in the R8/GALA-MENDSUV, the luciferase knockdown effect was significantly increased compared to STR-R8/5iRNA condensed complexes in time and dose dependent manners. Quantification of the released siRNA from the condensed complexes demonstrated that only the STR-H8/5iRNA released significant levels of siRNA at pH = 7.4, the pH of cytoplasmic, compared with STR-R8/5iRNA condensed complexes. In addition, imaging studies indicated that STR-H8/siRNA facilitated siRNA release. Collectively, these data reveal the importance of the controlled release of siRNA to the cytoplasm. (C) 2012 Elsevier Ltd. All rights reserved.
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