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The role of osmotic polysorbitol-based transporter in RNAi silencing via caveolae-mediated endocytosis and COX-2 expression

Paper ID Volume ID Publish Year Pages File Format Full-Text
7079 533 2012 13 PDF Available
Title
The role of osmotic polysorbitol-based transporter in RNAi silencing via caveolae-mediated endocytosis and COX-2 expression
Abstract

Polymeric diversity allows us to design gene carriers as an alternative to viral vectors, control cellular uptake, target intracellular molecules, and improve transfection and silencing capacity. Recently, we developed a polysorbitol-based osmotically active transporter (PSOAT), which exhibits several interesting mechanisms to accelerate gene delivery into cells. Herein, we report the efficacy of using the PSOAT system for small interfering RNA (siRNA) delivery and its specific mechanism for cellular uptake to accelerate targeted gene silencing. We found that PSOAT functioned via a caveolae-mediated uptake mechanism due to hyperosmotic activity of the transporter. Moreover, this selective caveolae-mediated endocytosis of the polyplexes (PSOAT/siRNA) was regulated coincidently with the expression of caveolin (Cav)-1 and cyclooxygenase (COX)-2. Interestingly, COX-2 expression decreased dramatically over time due to degradation by the constant expression of Cav-1, as confirmed by high COX-2 expression after the inhibition of Cav-1, suggesting that PSOAT-mediated induction of Cav-1 directly influenced the selective caveolae-mediated endocytosis of the polyplexes. Furthermore, COX-2 expression was involved in the initial phase for rapid caveolae endocytic uptake of the particles synergistically with Cav-1, resulting in accelerated PSOAT-mediated target gene silencing.

Keywords
RNAi silencing; Polysorbitol; Transporter; Caveolae-mediated endocytosis; Cav-1; COX-2
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The role of osmotic polysorbitol-based transporter in RNAi silencing via caveolae-mediated endocytosis and COX-2 expression
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 34, December 2012, Pages 8868–8880
Authors
, , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us