Fighting liver fibrosis with bio-guided drug delivery vehicles

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As part of an extensive, world-leading oncology research programme, The Second Affiliated Hospital Zhejiang University School of Medicine (SAHZU) in Hangzhou, China, has made breakthroughs in nanoparticle drug delivery systems for treating liver cancer and fibrosis, an inflammatory condition that precedes cancer.

Liver fibrosis is scarring caused by most types of chronic liver disease for which there is very little effective clinical treatment, says Weilin Wang, a surgeon and president of SAHZU. These scars impede the liver’s ability to remove waste from blood, metabolize nutrients and filter toxins.

The hormone melatonin could help limit scarring, says Wang. Melatonin aids the scavenging of free radicals, which helps prevent oxidative damage to cells, and also inhibits a key sensor involved in the inflammatory processes that can cause liver fibrosis, known as activating transcription factor 6.

However, ingested melatonin exhibits low bioavailability, and standard treatments are limited, so Wang’s team developed two pioneering nanoparticle drug delivery systems that use cell membrane coatings for precision targeting.

The first coating uses the membranes of hepatic stellate cells, which are key to the liver’s response to injuries. When activated, these membranes express a receptor that homes in on and binds to highly expressed platelet-derived growth factors in fibrotic livers.

The other coating is a membrane isolated from blood platelets, which can target inflammation. The CD47 protein on the membrane surface also helps prevent the treatment being destroyed by the immune system.

In experiments on mice1, both delivery methods improved the effects of melatonin.


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