Many chemotherapeutic agents used to treat cancer are associated with side effects of varying severity, as they are toxic to normal cells as well as malignant tumors. This has led to the discovery of effective alternatives to synthetic pharmaceuticals with which most cancers are currently treated.
The use of calcium phosphate and citrate for this purpose has been under discussion for the past few years, as they cause cell death when they reach directly into cells, while their presence in circulation has little or no toxic effect. The problem lies in the mechanism of finding ways to overcome the compounds that control the uptake of these compounds into cells, and ensure that the compounds act selectively on the cells they want to eliminate.
Dr. Constantin von Schirding, dau. Hanna Engelke and Proc. Researchers in the chemistry department at LMU, led by Thomas Bein, now report the development of a class of novel amorphous nanoparticles made of calcium and citrate, which are capable of dissolving. Barriers to elevate and kill tumor cells in a targeted fashion.
Both calcium phosphate and citrate are involved in the regulation of many cellular signaling pathways. Therefore, to avoid dissolution of these pathways, the levels of these substances present in the cytoplasm are tightly controlled.
Critically, the nanoparticles described in the new study are capable of bypassing these regulatory controls. “We have prepared amorphous and porous nanoparticles from calcium phosphate and citrate, which are encapsulated in a lipid layer,” von Schirding explains.
Encapsulation ensures that these particles are easily taken up by cells without triggering countermeasures. Once inside the cell, the lipid layer efficiently breaks down, and large amounts of calcium and citrate accumulate in the cytoplasm.
Experiments on cultured cells have shown that particles are selectively lethal — killing cancer cells, but essentially unbalancing healthy cells (which also ingest particles). “Clearly, particles can be highly toxic to cancer cells. In fact, we found that the more invasive the tumor, the greater the killing effect”, Engelke says.
During cellular lifting, nanoparticles acquire a second membrane coat. The authors of the study state that an unknown mechanism — specific to cancer cells — causes the rupture of this outer membrane, causing the contents of vesicles to leak into the cytoplasm.
On the other hand, in healthy cells, this outermost layer maintains its integrity, and the vesicles are subsequently retained in the extracellular medium.
“Highly selective toxicity of particles made it possible for us to successfully treat two different types of highly invasive pleurisy in mice. With only two doses, administered locally, we can reduce tumor size by up to 40 and 70%, respectively. Were able to reduce. ”Engelke says.
Many pleural tumors are metastatic products of lung tumors, and they develop in the pleural cavity between the pleural and the ribs. Because blood is not supplied in this area, it is inaccessible to chemotherapeutic agents. “In contrast, our nanoparticles can be introduced directly into the pleural cavity,” Bein says.
In addition, during two months of treatment, no signs of serious side effects were found. Overall, these results suggest that new nanoparticles have considerable potential for further development of novel treatments for other types of cancer.