Metal-enhanced photo-oxidation as a potential cancer treatment
Photodynamic therapy, an existing cancer treatment approach, uses photosensitisers to generate reactive oxygen species which when irradiated by light, selectively kill cancer cells. However, most existing photodynamic therapies rely on the presence of oxygen, while solid cancer tumours often feature a hypoxic microenvironment with very low oxygen levels, limiting the therapeutic efficiency of this approach.
To address this limitation, a research team led by Professor Zhu Guangyu, in the Department of Chemistry, and Professor He Mingliang, in the Department of Biomedical Sciences (BMS) at CityU, discovered an effect called metal-enhanced photo-oxidation. By conjugating metals like platinum with organic photosensitive ligands, they significantly enhanced the photo-oxidation capability. This led them to develop a new class of near-infrared-activated platinum photo-oxidants that can be activated by near-infrared light to directly oxidise biomolecules and effectively kill cancer cells without the need for oxygen.
The results demonstrated a significant reduction in tumour volume and weight of 89% and 76%, respectively, indicating the potent tumour-inhibitory effect of the photo-oxidants.
“Intriguingly, we found that the death mode of cancer cells induced by the photo-oxidants differs from that of any other anticancer agents,” said 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 experimental data show that after the photo-oxidants vigorously oxidised crucial biomolecules inside the cancer cells without requiring oxygen, generating reactive oxygen species, lipid peroxides and protons. The reactive oxygen species and lipid peroxides triggered intensive oxidative bursts, while the protons lowered the intracellular pH value, creating an unfavourable acidic microenvironment for the cancer cells.
The experiments confirmed that the platinum photo-oxidants effectively activate the immune system in both in vitro and in vivo settings. The number of T helper and T killer cells, which help to trigger the body’s immune response, increased by 7- and 23-fold, respectively, compared to the control group.
“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 He.
The work was published in Nature Chemistry.