Targeted delivery of diagnostic agents by surface-modified liposomes

Surface-modified LS have been used for the specific delivery of heavy metal-based imaging agents. The liposome surface was modified with PEG, AMmAb, Dext-SA, chelating agent DTPA-PE, and with NGPE-modified chelating polymer: DTPA-NPLL-NGPE. The hypothesis is suggested attempting to explain the phenomenon of long circulation of PEG-coated LS from the point of view of statistical properties of flexible polymer molecule in solution. Direct experiments using fluorescent labels were performed to prove the hypothesis. The calculations performed on the basis of the hypothesis were designed to find the optimal concentration of PEG on the LS surface, and suggested that it not only provides a protective effect but also does not create steric hindrances for the surface-immobilized mAb. As a result, long circulating targeted ILS have been prepared. Intravenously administered ¹¹¹In-labelled PEG-AMmAb-LS were targeted to the area of experimental myocardial infarction in rabbits under γ-scintigraphic control. Infarct-to-normal ratios of ¹¹¹In radioactivity of about 20 were achieved. PEG-and Dext-modified liposomes with surface-incorporated Gd-labelled DTPA-PE or DTPA-NPLL-NGPE were used for the subcutaneous administration and subsequent NMR-imaging of lymph nodes in rabbits. Two mechanisms of MR-signal enhancement were found for the surface-modified Gd-containing LS: the increase in signal intensity due to the increase in water quantity in the vicinity of Gd atoms because of PEG-associated water; and better lymph node accumulation of Dext-LS via receptor-mediated endocytosis. Surface modification of LS opens the possibilitiy for targeted delivery of heavy metal-based imaging agents.