Organic-inorganic hybrid-nanocarrier of siRNA constructing through the self-assembly of calcium phosphate and PEG-based block aniomer.
The development of siRNA delivery systems is a major key for practical RNA therapy that holds promise for the treatment of life-threatening human diseases, yet there still exists significant difficulties in their construction because of the various requirements including high transfection efficacy, tolerability in the biological medium, and low toxicity. Here we report the novel preparation route of organic-inorganic hybrid-nanocarriers entrapping siRNA based on the self-assembly of the block aniomer, poly(ethylene glycol)-block-poly(methacrylic acid), with calcium phosphate crystals. The nanocarriers have diameters in the range of several hundreds of nanometers and revealed excellent colloidal stability due to the steric stabilization effect of the PEG palisade. The biological activity of siRNA loaded in nanocarriers was assessed using 293 cells stably expressing luciferase gene, showing the remarkably high gene silencing-efficacy without the use of any adjuvant molecules such as chroloquin. Further advantage of the system is the serum tolerability, which is of a critical issue in in vivo application.
Kakizawa
Yoshinori
Y
Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
Furukawa
Sanae
S
Ishii
Atushi
A
Kataoka
Kazunori
K
D002130:Calcium Phosphates / Q000737:chemistry*; D002460:Cell Line; D015316:Genetic Therapy; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection / Q000379:methods
D002130:Calcium Phosphates; D011108:Polymers; D011109:Polymethacrylic Acids; D034741:RNA, Small Interfering; C099679:poly(methacrylic acid-ethylene glycol); D011092:Polyethylene Glycols; C020243:calcium phosphate; D008156:Luciferases