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 rats can enhance the phagocytic clearance capacity of tissue macrophages, particularly those of the liver and the spleen. Such stimulated cells were able to clear a significant portion of intravenously injected methoxypoly(ethyleneglycol)2000 liposomes (mean size of 87 nm), labelled with technetium-99m via the N-hydroxysuccinimidyl hydrazine nicotinate hydrochloride derivative of distearoyl phosphatidylethanolamine, within 4 h post administration. These liposomes, otherwise, exhibit long circulatory behaviour in control animals, with poor localization to the liver and spleen. We suggest that such technetium-99m-labelled engineered vesicles may be of aid for detection of the liver and spleen macrophages with enhanced phagocytic clearance capacity by gamma scintigraphy. Alterations in the phagocytic activity of liver and spleen macrophages is known to occur during cancer. Therefore, such diagnostic procedures may prove useful for patient selection or for monitoring the progress of treatment with long circulating nanoparticles carrying anti-cancer agents, thus minimizing damage to this important line of body's defence cells, and are discussed.
Laverman
P
P
Department of Nuclear Medicine, University Medical Center Nijmegen, The Netherlands.
Carstens
M G
MG
Storm
G
G
Moghimi
S M
SM
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers; D005029:Ethylenediamines / Q000494:pharmacology; D006321:Heart / Q000000981:diagnostic imaging; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics*; D008099:Liver / Q000000981:diagnostic imaging / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000502:physiology; D015609:Organotechnetium Compounds / Q000737:chemistry; D010316:Particle Size; D010587:Phagocytosis; D011092:Polyethylene Glycols / Q000494:pharmacology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D012588:Scintillation Counting; D013154:Spleen / Q000000981:diagnostic imaging / Q000276:immunology; D013501:Surface-Active Agents / Q000494:pharmacology; D013997:Time Factors; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005029:Ethylenediamines; D008081:Liposomes; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D013501:Surface-Active Agents; C012571:tetronic 701; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol