Scientists have come up with a unique way to kill cancer cells using light and oxygen
Researchers at City University of Hong Kong have developed a new platinum-enhanced, light-activated anticancer agent.Scientists have developed a new platinum-enhanced, light-activated compound. It kills cancer cells in a unique way, without requiring oxygen. The drug overcomes the limitations of existing light-based cancer therapies. This discovery could lead to the development of a new generation of anti-cancer drugs.
Photodynamic therapy (PDT) involves the administration of a photosensitizing agent, which is then activated by light energy of a specific wavelength, usually a laser or LED. The light activation generates reactive oxygen species (ROS), which damage cancer cells by triggering the process of apoptosis, or programmed cell death.
Although PDT has proven effective in treating cancer, the problem is that the presence of oxygen is required to generate the AFCs. Most solid tumors are characterized by a hypoxic (low-oxygen) microenvironment, and this reduces the effectiveness of conventional photosensitizers.
To overcome this limitation, researchers at City University of Hong Kong have developed a novel platinum-enhanced, light-activated agent that effectively kills cancer cells without requiring oxygen.
Platinum(IV) or Pt(IV) is a prodrug, which means it is pharmacologically inactive until it is metabolized when it reaches cancer cells. Previous studies have shown that adding transition metals such as platinum to photosensitizers increases their efficacy. The authors of the new study conjugated Pt(IV) complexes with organic photosensitizing ligands. They found that this leads to metal-enhanced photooxidation. This discovery led them to develop a new class of near-infrared-activated Pt(IV) photooxidizers.
The scientists injected the new compound into mice with tumors intravenously. Four hours later, they applied near-infrared light (NIR) to the mice to activate the photooxidants. This turned out to result in an 89% reduction in tumor volume and a 76% reduction in tumor weight, indicating an effect of cancer inhibition by the photooxidant Pt(IV). While traditional platinum-based anticancer drugs induce apoptosis of cancer cells, the new compound leads to a unique form of cell death.
"Interestingly, we found that the 'mode of death' of cancer cells induced by Pt(IV) photooxidants is different from the mode of death of any other anticancer agents. The unique mode of cancer cell destruction was initiated through a dual-action effect: strong intracellular oxidative stress and a decrease in intracellular pH value," explains Guangyu Zhu, an author of the study.
After Pt(IV) photooxidants that had accumulated in the endoplasmic reticulum of cancer cells (the center of protein synthesis and transport) were activated by NIR light, they oxidized biomolecules inside the cells without requiring oxygen, producing AFCs, lipid peroxides and protons. AFCs and lipid peroxides lead to oxidative "bursts" that damage important components of cancer cells, while protons lower intracellular pH, creating an unfavorable acidic microenvironment.
In addition, the researchers observed that Pt(IV) photooxidants activated the immune system of the mice by recruiting and activating immune cells. Compared to the control group, the number of T-helper cells increased sevenfold and the number of cytotoxic T cells increased 23-fold after light activation. Cytotoxic T cells, or T-killers, recognize and destroy cancer cells directly, while T-helpers help activate cytotoxic T cells.
The study is published in the journal Nature Chemistry.