Antitumor agents are required to destroy cancer cells without causing any harm to healthy tissue, while also avoiding any toxic side-effects. Researchers from the University of Science and Technology of China have developed a new approach using “self-immolative” polyferrocenes, which are copolymers that split apart into their components as soon as they enter a tumor cell. These drugs then synergistically cause a sudden increase in free radicals, which incapacitate the defenses of tumor cells, without harming healthy tissue.
The Science Behind the Self-Immolative Polymers
The research team led by Xianglong Hu and Shiyong Liu at the University of Science and Technology of China has incorporated two synergistically cooperative molecules into a copolymer. The copolymer chains are hydrophobic on one end and hydrophilic on the other. When placed in aqueous environments, they aggregate into nanoparticles. The hydrophobic ends of the chains split apart into their individual building blocks, which are made from azaquinone methide (AQM) units carrying aminoferrocene sidechains, only in the significantly more acidic environment of tumor cells.
Glutathione is subsequently activated within the tumor cells, attacking the azaquinone methide units, binding to them, and splitting off the iron sandwiches. The complex then reacts with hydrogen peroxide (H2O2) present in the cells to form hydroxyl radicals (•OH). In this process, the divalent iron in the complex is oxidized to trivalent iron, which the glutathione reduces back to FeII. This fatal cycle consumes the glutathione and abruptly produces a high concentration of hydroxyl radicals in the cell.
Efficient Inhibition of Tumor Growth
Experiments were performed by the research team both in vitro and in mice with tumors to demonstrate the effectiveness of the self-immolative polymers. The results showed that this approach efficiently inhibited tumor growth with negligible side-effects. The nanoparticles remain intact and inactive in healthy tissues, only being activated in the acidic environment of tumor cells. The polyethylene glycol layer prevents the nanoparticles from being rapidly broken up in the blood by components of the immune system.
This new approach could allow for new possibilities in the chemodynamic therapy (CDT) of tumors. The synergy of these two processes puts the tumor cells under severe oxidative stress, which damages and kills them. The copolymers could be used as antitumor agents, destroying cancer cells while protecting healthy tissue and avoiding any toxic side-effects.
The development of self-immolative polymers marks a significant advancement in the treatment of cancer. While more research is needed, this approach has the potential to revolutionize cancer treatment and improve the quality of life for those suffering from this disease.
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