Lipid Nanoparticles Carrying Calcium Phosphate and Citrate are Selectively Toxic to Cancer Cells

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Researchers here note an approach to destructively destabilizing the metabolism of cancer cells via lipid nanoparticle delivery of calcium phosphate and citrate. The precise details of the mechanisms by which cancer cells are specifically vulnerable to this mode of delivery, while normal cells essentially reject the nanoparticles, are presently unknown. That will likely limit the further development of this approach to therapy until there is a greater understanding of how exactly it works, even given the promising initial results in mice.

Researchers have developed a novel type of nanoparticle that efficiently and selectively kills cancer cells, thus opening up new therapeutic options for the treatment of tumors. Both calcium phosphate and citrate are involved in the regulation of many cellular signaling pathways. Hence, the levels of these substances present in the cytoplasm are tightly controlled, in order to avoid disruption of these pathways. Crucially, the nanoparticles described in the new study are able to bypass these regulatory controls. Researchers repared amorphous and porous nanoparticles consisting of calcium phosphate and citrate, which are encapsulated in a lipid layer. The encapsulation ensures that these particles are readily taken up by cells without triggering countermeasures. Once inside the cell, the lipid layer is efficiently broken down, and large amounts of calcium and citrate are deposited in the cytoplasm.

Experiments on cultured cells revealed that the particles are selectively lethal - killing cancer cells, but leaving healthy cells (which also take up particles) essentially unscathed. During cellular uptake, the nanoparticles acquire a second membrane coat. The authors of the study postulate that an unknown mechanism - which is specific to cancer cells - causes a rupture of this outer membrane, allowing the contents of the vesicles to leak into the cytoplasm. In healthy cells, on the other hand, this outermost layer retains its integrity, and the vesicles are subsequently excreted intact into the extracellular medium.

"The highly selective toxicity of the particles made it possible for us to successfully treat two different types of highly aggressive pleural tumors in mice. With only two doses, administered locally, we were able to reduce tumor sizes by 40 and 70%, respectively. Furthermore, over the course of a 2-month treatment, no signs of serious side-effects were detected."

Link: https://www.en.uni-muenchen.de/news/newsarchiv/2020/engelke_nanoparticles.html

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source https://www.fightaging.org/archives/2020/12/lipid-nanoparticles-carrying-calcium-phosphate-and-citrate-are-selectively-toxic-to-cancer-cells/