A City University of Hong Kong research team has developed near-infrared-activated photo-oxidants that may kill cancer cells without the use of oxygen, presenting a promising "photo-oxidation therapy" for overcoming cancer cell resistance.

They improved this technique by employing metal-conjugated organic molecules, which led to the invention of platinum(IV) photo-oxidants triggered by near-infrared light, which were shown to be extremely successful in lowering tumor volume and weight in animal studies.

“Intriguingly, we found that the ‘death mode’ of cancer cells induced by the Pt(IV) photo-oxidants differs from that of any other anticancer agents,” said Professor Zhu. “A unique mode of cancer cell destruction was initiated through the dual-action effect of strong intracellular oxidative stress and reduced intracellular pH value.”

Their research demonstrates that Pt(IV) photo-oxidants, activated by near-infrared radiation within cancer cell endoplasmic reticulum, vigorously oxidize biomolecules, producing ROSs, lipid peroxides, and protons, independent of oxygen.

Pt(IV) photo-oxidants induce oxidative reactions and an acidic environment, making them hostile to cancer cells. They also boost the immune system, causing immunogenic cell death and increasing T helper and T killer cell counts in mice.

“By inducing nonclassical necrosis, Pt(IV) photo-oxidants can overcome the resistance of cancer cells to traditional photodynamic therapies and chemotherapy agents, activate the immune system, and effectively eliminate cancer cells,” explained Professor Zhu.

“These findings serve as proof of concept and suggest that the development of photo-oxidants based on metal-enhanced photo-oxidation is a promising new direction for developing metal-based anticancer drugs,” said Professor He.

The research team plans preclinical investigations to thoroughly assess the chemical, biological, and pharmaceutical properties of the newly developed Pt(IV) photo-oxidants, with the ultimate goal of identifying lead compounds for clinical trials. Co-first authors, Dr. Deng Zhiqin and Dr. Li Huangcan, are affiliated with CityU. Corresponding authors are Professors Zhu and He. Collaborators from CityU include Professors Michael Yang Mengsu, Lu Jian, Li Yangyang, Lo Pui-chi, Lei Dangyuan, Dr. Ou Weihui, Dr. Wang Na, Dr. Chen Shu, and PhD students Liu Gongyuan, Xu Feijie, and Wang Xiong.

Funding for the study came from sources such as the Hong Kong Research Grants Council, National Natural Science Foundation of China, and Science Technology and Innovation Committee of Shenzhen Municipality.