Calcium Bomb
Multidrug resistance, the process by which tumors become resistant to drugs, is the main cause of cancer chemotherapy failures. Tumor cells often acquire multidrug resistance with the help of proteins that remove drugs from the cell, making chemotherapy ineffective. Researchers representing the American Chemical Society have developed nanoparticles that trigger the release of calcium inside tumor cells, inhibiting drug pumps and eliminating multidrug resistance.
The tumor protein P-glycoprotein (P-gp) often plays a key role in the development of drug resistance. It is located in the cell membrane and uses energy in the form of adenosine triphosphate (ATP) to pump drugs out of tumor cells. Scientists have previously tried to block P-gp in various ways, for example, using low-molecular-weight inhibitors or by depletion of ATP reserves. However, the strategies that exist so far are associated with serious side effects or are ineffective in the body. Some treatments are too difficult to implement. In this study, the group tried to block P-gp using a different approach.
Previous studies have shown that overloading tumor cells with calcium ions can reduce the production of P-gp and reduce ATP levels. But it was important to find a way to deliver a "calcium bomb" together with a chemotherapeutic drug inside cancer cells.
The researchers created the so-called calcium ion nanogenerator (TCaNG) by loading the chemotherapeutic drug doxorubicin onto calcium phosphate nanoparticles, and then coating them with molecules that will allow TCaNG to find and penetrate cancer cells.
Once inside the cells, TCaNG decompose in the acidic environment of lysosomes, releasing doxorubicin and at the same time a large amount of calcium ions.
Multidrug resistance is eliminated due to the specific accumulation of calcium in the mitochondria, where it suppresses cellular respiration and causes tumor hypoxia, which leads to a sharp decrease in the synthesis of P-gp. In addition, respiratory suppression blocks intracellular ATP production, and this further leads to the failure of P-gp.
The team tested TCaNG on cancer cells in vitro and found that the production of both ATP and P-gp decreased, which allowed doxorubicin to destroy previously resistant tumor cells. When testing im vivo in mice treated with TCaNG, after 21 days of therapy, a significant decrease in tumor size (approximately 13 times, and without pronounced side effects) was observed compared to the control group.
This simple, safe and effective method of "calcium explosion" has the potential for clinical use in the treatment of tumors.
Article J.Liu et al. Nanoenabled Intracellular Calcium Bursting for Safe and Efficient Reversal of Drug Resistance in Tumor Cells is published in the journal Nano Letters.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on ACS materials: Calcium bursts kill drug-resistant tumor cells.