Zero damage to normal cells, a new type of nano weapon that accurately strikes cancer cells
Medical profession
Science and Technology Daily (Reporter Chen Xi, correspondent Ren Yang Hao Chuwei) Traditional cancer chemotherapy has a series of problems in terms of targeting, drug resistance, side effects, metastasis and recurrence.
Recently, the team of Yanjun Zhao and Zheng Wang of the School of Pharmaceutical Science and Technology of Tianjin University designed a new type of nano-drug carrier based on the mechanism of cell iron death. It has the characteristics of selectivity and broad-spectrum, and is expected to be "zero damage" to normal cells. Under the premise, the efficient elimination of solid tumor cells, related research results published in the "American Chemical Society Nano Research" (ACS Nano) magazine, bring new hope for humans to overcome cancer.
Iron death is a new type of iron ion-dependent cell death. Its morphological, biochemical, and genetic characteristics are different from other cell death pathways such as apoptosis and autophagy. The specific feature is the imbalance of intracellular redox homeostasis.
Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is one of the key molecules to maintain intracellular redox homeostasis. Researchers have found that selective depletion of NADPH in tumor cells can enhance tumor cell iron death.
The team of Professor Yanjun Zhao and Professor Wang Zheng designed a polymer nanomicelle carrier, which contains two functional groups "azobenzene" and "nitroimidazole". It has dual hypoxia sensitivity and can enhance the effect of cell iron death. .
At the same time, a small molecule iron death inducer is contained in the nanomicelles to selectively attack cancer cells.
The team used mouse breast cancer cells as a model. The experimental results showed that this polymer carrier can not only enhance the drug uptake of tumor cells and realize the controllable release of drugs in the cells, but also consume a large amount of NADPH in tumor cells, thereby increasing Sensitive tumor cells die of iron.
According to the team, due to the obvious difference in oxygen concentration between hypoxic solid tumors and normoxic normal tissues, the iron death sensitization effect of this type of carrier is limited to tumor cells and has almost no toxicity to normal cells.
This achievement has three advantages: selectivity, distinguishing tumor tissue from normal organs/tissues based on whether hypoxia can reduce "injury" to healthy cells; broad-spectrum, curative effect on various hypoxic solid tumors; Drug resistance, highly sensitive to drug-resistant cells based on apoptosis mechanism.