As mentioned earlier, there are few if any reports about cation polymers as carriers for COX-2 siRNA delivery. Here we used PEGylated PEI, a common cationic polymer applied in siRNA transfection [, ] as a control. PEI increased the expression of COX-2 to such an extent that it offset downregulation caused by siRNA. Our degradable compound 4 was cleaved to release amine groups with positive charge. Compared to macromolecules, the small molecules with amine groups were rapidly removed from cells. These detached amine groups were distributed more uniformly in the cytoplasm, which reduced positive charge density. Due to high biocompatibility, although the dextran scaffold was depolymerized to small molecules by α-1-glucosidases present in cells and various organs, their retention in cells did not affect COX-2 expression. Consequently, our degradable compound 4 minimized inflammation, and was able to downregulate COX-2 successfully.
The results demonstrate that both siRNA reagents (at 20 nM) decrease the expression of the targeted MAPK14 gene by at least 70 percent. Neither siRNA method affects the expression of GAPD. However, the synthetic siRNA also non-specifically decreases the expression of RRAD and increases the expression of CTGF, even at the lower concentration (5 nM). The enzymatically-generated population does not affect the expression of these genes even at the higher concentration (20 nM). The reproducible results achieved for this single gene support the hypothesis that enzymatically generated siRNA more specifically knocks down the expression of the targeted gene than chemically synthesized siRNA.
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113. Patil ML, Zhang M, Minko T. Multifunctional Triblock Nanocarrier (PAMAM-PEG-PLL) for the Efficient Intracellular siRNA Delivery and Gene Silencing. 2011;5:1877-1887
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120. Gabrielson NP, Lu H, Yin L, Kim KH, Cheng J. A cell-penetrating helical polymer for siRNA delivery to mammalian cells. 2012;20:1599-1609
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106. Zhang LM, Lu ZX, Zhao QH, Huang J, Shen H, Zhang ZJ. Enhanced Chemotherapy Efficacy by Sequential Delivery of siRNA and Anticancer Drugs Using PEI-Grafted Graphene Oxide. 2011;7:460-464
Improve Existing Aptamers & siRNA
96. Podesta JE, Al-Jamal KT, Herrero MA, Tian BW, Ali-Boucetta H, Hegde V. . Antitumor Activity and Prolonged Survival by Carbon-Nanotube-Mediated Therapeutic siRNA Silencing in a Human Lung Xenograft Model. 2009;5:1176-1185