Recognition and clearance of methoxypoly(ethyleneglycol)2000-grafted liposomes by macrophages with enhanced phagocytic capacity - Implications in experimental and clinical oncology

Intravenous injection of an endotoxin-free solution of poloxamine-908 to ra ts can enhance the phagocytic clearance capacity of tissue macrophages, par ticularly those of the liver and the spleen. Such stimulated cells were abl e to clear a significant portion of intravenously injected methoxypoly(ethy leneglycol)2000 liposomes (mean size of 87 nm), labelled with technetium-99 m via the N-hydroxysuccinimidyl hydrazine nicotinate hydrochloride derivati ve of distearoyl phosphatidylethanolamine, within 4 h post administration. These liposomes, otherwise, exhibit long circulatory behaviour in control a nimals, with poor localization to the liver and spleen. We suggest that suc h technetium-99m-labelled engineered vesicles may be of aid for detection o f the liver and spleen macrophages with enhanced phagocytic clearance capac ity by gamma scintigraphy. Alterations in the phagocytic activity of liver and spleen macrophages is known to occur during cancer. Therefore, such dia gnostic procedures may prove useful for patient selection or for monitoring the progress of treatment with long circulating nanoparticles carrying ant i-cancer agents, thus minimizing damage to this important line of body's de fence cells, and are discussed. (C) 2001 Elsevier Science B.V. All rights r eserved.