THE STUDY OF SELECTIVE DEPLETION OF MONOCYTES/MACROPHAGES BY LIPOSOME ENCAPSULATED CLODRONATE
- VernacularTitle:脂质体包裹Clodronate对单核/巨噬细胞选择性清除作用的研究
- Author:
Jianchuan GAO
;
Jiake CHAI
;
Huinan YIN
- Publication Type:Journal Article
- Keywords:
liposomes;
clodronate;
monocytes;
macrophages
- From:
Medical Journal of Chinese People's Liberation Army
2001;0(10):-
- CountryChina
- Language:Chinese
-
Abstract:
Free clodronate has a very poor ability to permeate cell membrane and an extremely short half-life in circulation. However, it can be encapsulated with liposomes, and then can be phagocytosed by monocytes/macrophages. Clodronate is released in the cells and be metabolized to a toxic ATP analog. By this way, monocytes/macrophages can be effectively depleted. The study showed that the prepared liposomes had a negative charge (-40mV) on the surface and a high encapsulation efficiency of clodronate (17.6%～19.0%) with an average size of 200nm. The spherical shape of liposome was confirmed both by transmission electron microscope and laser scanning confocal microscope. Neither free clodronate nor liposome clodronate inhibited vascular endothelial cell and smooth muscle cell proliferation. Clodronate, once encapsulated in liposomes, significantly reduced macrophage proliferation in a dose dependent manner, while free clodronate or empty liposomes had no effect on macrophages. With laser scanning confocal microscope observation, rhodamine labeled liposomes were found to penetrate and accumulate inside monocytes and macrophages, but not into the smooth muscle cells. Furthermore, rhodamine labeled liposomes without encapsulating clodronate was found to accumulate inside macrophages, but causing no damage to cells. The macrophages which engulfed rhodamine labeled clodronate liposomes would manifest a morphological structure resembling apoptotic state. The results suggest that monocytes/macrophages can be depleted via phagocytosis of liposome encapsulated clodronate without affecting non-phagocytotic cells.
