Red light-activated anti-cancer treatment

By : Michael Gibb

But an anti-cancer chemical compound developed by Dr Zhu Guangyu, Associate Professor in the Department of Chemistry, offers hope for minimising the degree of damage that “normal” cells undergo during cancer treatment.

“Phorbiplatin, the new chemical compound we’re working on for tackling cancer, shows great promise,” explains Dr Zhu, who researches anti-cancer drug development, drug mechanism and target validation, drug delivery, photodynamic therapy and chemical biology. A US patent for phorbiplatin is currently pending.

“This new treatment offers a more efficient and effective means to trigger anti-cancer drug activation in the tumour,” he says.

 

 

 

The process makes use of red light to fight tumours, a form of treatment that has gained prominence in recent years. It works like this. Dr Zhu and his team functionalise the anti-cancer drug oxaliplatin with a photoabsorber that is highly sensitive to red light. The photoabsorber is then activated using low intensity red light that activates the anti-cancer agents in the body.

Red light is favoured because it enables deeper penetration and doesn’t harm non-cancerous cells, whereas ultraviolet light has a relatively weaker penetration capacity and can damage cells.  

“Phorbiplatin is also very promising because when it is in the dark, for example when the agent is within the body, it remains inactive. Then, using low-power red-light irradiation, without resorting to any kind of external catalyst, the phorbiplatin can be activated,” says Dr Zhu.

Phorbiplatin can be activated by low-power red-light irradiation.“Essentially phorbiplatin is the first small-molecule platinum (IV) prodrug that can be activated by a red light,” he adds. A prodrug is one that the body metabolises after it enters the body and becomes an active pharmacological drug. Platinum-based anti-cancer drugs including cisplatin and oxaliplatin are used in more than half of chemotherapy treatments in the clinic.

“It took us around three years to develop phorbiplatin,” says Dr Zhu, whose lab, the Zhu Group, focuses on what lies at the interface of chemistry and biology in the study of the mechanisms of anti-cancer drugs, especially metal-based drugs, and the development of innovative anti-cancer complexes, such as nanomedicine and chemo-immunotherapeutic agents.

“Getting the right balance of chemicals was the tricky part,” he says.

“This new treatment offers a more efficient and effective means to trigger anti-cancer drug activation in the tumour.” So far tests on mice have revealed good news. Dr Zhu’s new approach has “significantly improved anti-tumour activity”. Phorbiplatin triggered by red light appeared to result in a 67% reduction in tumour size and 62% reduction in weight compared with mice treated with oxaliplatin used in different forms and methods.

The CityU team also found that the major organs of the mice in the tests were in relatively good condition after treatment whereas mice treated with previous approaches using oxaliplatin suffered some side effects.

Dr Zhu Guangyu (front) and his research team.“Our aim is to use this research to contribute to the development of photoactivatable anti-cancer drugs, especially those that can be activated by red light, and reduce the toxicity seen in traditional chemotherapy. The team will work on pre-clinical studies and conduct more toxicity tests as well as efficacy tests,” Dr Zhu says.

The research findings for phorbiplatin have been published in the scientific journal Chem. The other team members include PhD student Wang Zhigang; Dr Ko Chi-chiu and Dr Hajime Hirao, Associate Professors in the Department of Chemistry; Dr Shi Peng, Associate Professor in the Department of Biomedical Engineering; and CityU researchers Wang Na, Cheng Shun-cheung, Xu Kai, Deng Zhiqin, Chen Shu, Xu Zoufeng, Xie Kai and Tse Man-kit.