Green-tea-based nanocarrier kills cancer cells more effectively

October 6, 2014

The two-step assembly process of a new anti-cancer drug-delivery system: (Left) Herceptin, a protein drug used to treat breast cancer, is combined with OEGCG, based on an ingredient of green tea. (Right) A protective shell containing “stealth” molecule PEG and EGCG (from green tea) is added (credit: IBN)

A drug-delivery system that may kill cancer cells more efficiently has been developed by Singapore researchers, using an antioxidant ingredient of green tea.

A key ingredient in green tea, epigallocatechin gallate (EGCG), is an antioxidant known to have therapeutic applications in the treatment of many disorders, including cancer. A*STAR’s Institute of Bioengineering and Nanotechnology (IBN) researchers have now engineered nanocarriers using EGCG that they say can deliver drugs and kill cancer cells more efficiently. Their work was published recently in Nature Nanotechnology.

“This is the first time that green tea has been used as a material to encapsulate and deliver drugs to cancer cells. Our green tea nanocarrier not only delivered protein drugs more effectively to the cancer cells; the combination of carrier and drug also dramatically reduced tumor growth compared with the drugs alone,” said Professor Jackie Y. Ying, IBN Executive Director.

A key challenge in chemotherapy is ensuring that the drugs are delivered only to the tumor to avoid harming the surrounding healthy tissues and organs. Researchers have developed drug carriers that specially target cancer cells. But these existing carriers limit the amount of drug a carrier can deliver, and are made of materials that themselves have no therapeutic effect — they may even cause side effects if used in large quantities, say the IBN researchers.

How it works

So IBN designed a therapeutic nanocarrier for drug delivery using novel compounds derived from EGCG as the core of this carrier to encapsulate drugs and proteins such as herceptin, a protein drug currently used to treat breast cancer. Here’s the recipe (referring to the diagram above):

  1. Combine herceptin (a protein drug used to treat breast cancer) with OEGCG (based on EGCG), creating a “micellar nanocomplex” that protects the protein drug from damage and removal by kidneys.
  2. Add a protective shell containing polyethylene glycol (PEG) combined with EGCG. (PEG is a “stealth” molecule that acts to camouflage the carrier, preventing it from being detected and filtered out of the body by the immune system before it reaches the tumor.)

The research team conducted animal studies to evaluate the nanocarrier, revealing that it reduced tumor growth much more effectively when compared to administering herceptin on its own: Twice as much herceptin drug accumulated in the cancer cells, suggesting improved tumor-targeting ability. Drug accumulation  was also lowered by 70% in the liver and kidney and by 40% in the lung.

IBN says it has filed a patent on the green tea nanocarrier and is developing it for clinical applications. IBN is also looking into personal care and nutritional products.

Abstract of Self-assembled micellar nanocomplexes comprising green tea catechin derivatives and protein drugs for cancer therapy

When designing drug carriers, the drug-to-carrier ratio is an important consideration, because the use of high quantities of carriers can result in toxicity as a consequence of poor metabolism and elimination of the carriers1. However, these issues would be of less concern if both the drug and carrier had therapeutic effects. (−)-Epigallocatechin-3-O-gallate (EGCG), a major ingredient of green tea, has been shown, for example, to possess anticancer effects234567, anti-HIV effects8, neuroprotective effects9 and DNA-protective effects10. Here, we show that sequential self-assembly of the EGCG derivative with anticancer proteins leads to the formation of stable micellar nanocomplexes, which have greater anticancer effects in vitro and in vivo than the free protein. The micellar nanocomplex is obtained by complexation of oligomerized EGCG with the anticancer protein Herceptin to form the core, followed by complexation of poly(ethylene glycol)–EGCG to form the shell. When injected into mice, the Herceptin-loaded micellar nanocomplex demonstrates better tumour selectivity and growth reduction, as well as longer blood half-life, than free Herceptin.