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Green Tea Compound Helps siRNA Slip Inside Cells

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It’s called a “green nanoparticle” – not because it arises in nature, but because it incorporates a metabolite, an antioxidant, that is found in green tea. The green nanoparticle’s other component, a small polymer, is not so natural. It is low in toxicity, however, and it can complex with the antioxidant to form a unique drug delivery vehicle, one that can carry delicate RNA drugs safely across the cell membrane.


By facilitating the efficiency of RNA drugs – specifically, small interfering RNAs (siRNAs) – the green nanoparticles may enhance green tea’s reputation as a promoter of good health. Already, the drinking of green tea has been linked to health benefits ranging from cardiovascular disease prevention to weight loss. Now, by contributing an antioxidant compound called epigallocatechin gallate (EGCG) to a siRNA delivery vehicle, green tea may be positioned to claim a share of the esteem that may, one day, be earned by siRNAs.



siRNAs have great therapeutic potential because they can dial down the expression of disease-related genes. However, getting siRNAs into cells, where they can do their job, has been challenging. Being relatively large and negatively charged, siRNAs cannot easily cross the cell membrane, and they are susceptible to degradation by RNA-chomping enzymes.


To overcome these problems, some researchers have tried coating siRNAs with various polymers. However, most small polymers can’t shuttle siRNAs into cells, whereas larger polymers can be effective but are generally toxic.


A new approach developed by scientists based at East China Normal University and South China University of Technology, however, appears to be more successful. These scientists, led by Yiyun Cheng, decided to use EGCG, which is known to bind strongly to RNA, in combination with a small polymer to form nanoparticles that safely deliver siRNA into cells.


Cheng and colleagues described their work in an article (“Green Tea Catechin Dramatically Promotes RNAi Mediated by Low-Molecular-Weight Polymers”) that appeared in the journal ACS Central Science.


“We report a facile strategy to fabricate core–shell-structured nanoparticles with robust siRNA delivery efficiency,” the article’s authors detailed. “The nanoparticle is prepared by entropy-driven complexation of siRNA with a green tea catechin to yield a negatively charged core, followed by coating low-molecular-weight polymers to form the shell.”


This supramolecular strategy, the authors declared, facilitates the polymers condensing siRNA into uniform nanoparticles. These nanoparticles, the authors continued, can specifically downregulate target genes in vitro and in vivo.


The nanoparticles efficiently knocked down the expression of several target genes in cultured cells, showing that the particles could cross the cell membrane. In a mouse model of intestinal injury, the nanoparticles were used to deliver an siRNA that targeted a pro-inflammatory enzyme. This intervention improved symptoms such as weight loss, shortening of the colon, and intestinal inflammation.


In addition to the gene-silencing effects of the siRNA, EGCG could contribute to the nanoparticles’ effectiveness through its antioxidant and anti-inflammatory properties, the researchers said.


“The highly efficient nanoparticles are applicable for various polymers with different topologies and chemical compositions, providing a versatile technique to break down the efficiency-toxicity correlation of cationic polymers,” the researchers concluded. “The proposed strategy in this study permits the development of a promising platform for polymer-mediated siRNA delivery.”

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