Green Tea Polyphenol Helps Therapeutic RNAs Slip Inside Cells

Epigallocatechin gallate (EGCG) is the major polyphenol in the leaves of green tea (Camellia sinensis). This compound is the subject of increasing research interest because it has demonstrated beneficial effects in studies of diabetes, Parkinson’s and Alzheimer’s diseases, stroke, and obesity. Now, a team of scientists in China has found a surprising use for EGCG — sneaking small interfering RNAs (siRNAs) into cells.

The green tea (Camellia sinensis). Image credit: Wilerson S. Andrade / CC BY-SA 2.0.

The green tea (Camellia sinensis). Image credit: Wilerson S. Andrade / CC BY-SA 2.0.

siRNAs have great potential to specifically down-regulate target genes for the treatment of various diseases.

However, getting siRNAs into cells where they can do their job has been challenging.

Being relatively large and negatively charged, they 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 research team led by Dr. Yiyun Cheng from the East China Normal University and the South China University of Technology wondered if they could 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.

Schematic illustration of ‘green’ nanoparticle formulation and the proposed gene silencing mechanism. Image credit: Shen et al, doi: 10.1021/acscentsci.8b00363.

Schematic illustration of ‘green’ nanoparticle formulation and the proposed gene silencing mechanism. Image credit: Shen et al, doi: 10.1021/acscentsci.8b00363.

The scientists made their nanoparticles by first combining EGCG and siRNA, which self-assembled into a negatively charged core.

Then, they coated this core with a shell consisting of a small, positively charged polymer.

These nanoparticles efficiently knocked down the expression of several target genes in cultured cells, showing that the particles could cross the cell membrane.

Next, Dr. Cheng’s team tested the nanoparticles in a mouse model of intestinal injury, using an siRNA that targeted a pro-inflammatory enzyme.

The nanoparticles 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 study authors said.

The study was published in the journal ACS Central Science.

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Wanwan Shen et al. Green Tea Catechin Dramatically Promotes RNAi Mediated by Low-Molecular-Weight Polymers. ACS Cent. Sci, published online September 19, 2018; doi: 10.1021/acscentsci.8b00363

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