Researchers from the City University of Hong Kong have developed a new, controllable cancer drug called phorbiplatin that only becomes active and potent after red light stimulation. Their work demonstrates that in the dark the cancer drug does not have substantial toxicity, but the drug is able to substantially reduce tumor size when activated by red light. One day, this technology may be used to improve cancer treatment and reduce its side effects.
Currently, many cancer drugs are administered and have toxic effects on both cancer cells and our body’s healthy cells. This leads to incredibly challenging side effects for those undergoing cancer treatment. To address this challenge, the researchers developed an inactive form of the cancer drug oxaliplatin, and engineered the molecule such that it would be activated under red light. Therefore, the inactive form would circulate throughout the body without damaging cells, and by stimulating with red light at the site of the tumor, the drug would be activated, killing only the tumor cells in that area.
The team validated the drug with multiple tests. First, they performed toxicity testing of the inactive pro-drug on human lung cells in a dish, and found there was no substantial toxicity. Then, they tested the pro-drug on cancer cells in a dish with red light stimulation and observed cancer cell killing, as they had desired. Finally, they performed mouse model testing, treating mice with cancer with their engineered pro-drug along with red light stimulation at the site of the tumor. They found substantial tumor reduction, even greater than what was observed by administering the chemotherapeutic active form of oxaliplatin.
“Under short-period irradiation with low intensity of red light (650 nm, 7 mW/cm2) and without any external catalyst, phorbiplatin is reduced to oxaliplatin, a first-line clinical chemotherapeutic drug, as well as pyropheophorbide a (PPA), a photoactivation ligand. Both substances are effective in killing tumor cells,” said Dr. Zhu Guangyu, the leader of the research. “Phorbiplatin is the first small-molecule platinum(IV) prodrug that can be activated by a red light.”
The publication in journal Chem: Phorbiplatin, a Highly Potent Pt(IV) Antitumor Prodrug That Can Be Controllably Activated by Red Light
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