氯膦酸二鈉脂質(zhì)體ClodronateLiposomes清除巨噬細胞英文介紹

Why use Clodronate Liposomes?

Macrophages play an important role in the host defense response and the regulation of many biological processes. Their main activity is phagocytosis and the production and release of soluble mediators (such as NO, cytokines, and chemokines).

Methods to manipulate macrophage activity through liposome-encapsulated molecules

*Drugs that interfere with cellular metabolic pathways can be encapsulated in liposomes, to study their effects on macrophages (drug methods).

*Drugs that selectively interfere with signaling pathways in macrophages can be encapsulated in liposomes

However, signal transduction pathways and compounds affecting these pathways are still under investigation. Therefore, so far, the former method is generally used to inhibit macrophage activity by administering liposome-encapsulated bisphosphonate clodronate.

How Do Clodronate Liposomes Induce Apoptosis in Phagocytes?

Once clodronate is encapsulated in liposomes, it can specifically target phagocytes. Liposomes can be quickly recognized and swallowed by macrophages, allowing an effective clodronate concentration threshold to trigger target cell apoptosis. Clodronate encapsulated in liposomes is recognized as a foreign body by phagocytes and is taken into internal vesicles called phagosomes. After phagocytosis, the phagosome fuses with the lysosome containing phospholipase, which destroys the phospholipid bilayer of the liposome, thereby allowing clodronate to be released in the cell. Once clodronate is released in the cytoplasm, aminoacyl-tRNA synthetase will mistakenly identify it as pyrophosphate and will use clodronate to generate the non-hydrolyzable ATP analogue (AppCCl2p). Then, this ATP analog translocates to the mitochondria, where it irreversibly binds to the ATP/ADP translocase, causing blockage of the respiratory chain, leading to changes in mitochondrial function and integrity. These altered mitochondria release molecular signals that will initiate cell apoptosis.

Unencapsulated clodronate cannot pass through the cell membrane to trigger cell death. Since the control liposome does not contain clodronate, the phagocytes will not be killed.