Interdepartmental Biological Sciences Program, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, USA.
Mol Pharm. 2011 Aug 1;8(4):1285-91. doi: 10.1021/mp200084y. Epub 2011 Jun 28.
Structural requirements of siRNA-functionalized gold nanoparticles (siRNA-Au NPs) for Dicer recognition and serum stability were studied. We show that the 3' overhang on the nucleic acids of these particles is preferentially recognized by Dicer but also makes the siRNA duplexes more susceptible to nonspecific serum degradation. Dicer and serum nucleases show lower preference for blunt duplexes as opposed to those with 3' overhangs. Importantly, gold nanoparticles functionalized with blunt duplexes with relatively less thermal breathing are up to 15 times more stable against serum degradation without compromising Dicer recognition. This increased stability leads to a 300% increase in cellular uptake of siRNA-Au NPs and improved gene knockdown.
研究了 siRNA 功能化金纳米颗粒（siRNA-Au NPs）的结构要求，以实现 Dicer 的识别和血清稳定性。我们表明，这些颗粒上的核酸 3'突出端优先被 Dicer 识别，但也使 siRNA 双链体更容易受到非特异性血清降解的影响。Dicer 和血清核酸酶对平端双链体的偏好低于 3'突出端的双链体。重要的是，用相对较少热呼吸的平端双链体功能化的金纳米颗粒对血清降解的稳定性提高了 15 倍，而不影响 Dicer 的识别。这种稳定性的提高导致 siRNA-Au NPs 的细胞摄取增加了 300%，基因敲低效果也得到了改善。
