Fc-Receptor-mediated Targeting of Antibody-bearing Liposomes Containing Dideoxycytidine Triphosphate to Human Monocyte/Macrophages

Abstract

Liposomes bearing surface-attached antibody (L-Ab) molecules can be used for various purposes including the immunospecific delivery of drugs or other materials to antigenic target cells. In this study, L-Ab were prepared to deliver an anti-human immunodeficiency virus (HIV) drug, dideoxycytidine triphosphate (ddCTP) to human monocyte/macrophages. Cells of the monocyte/macrophage lineage are an important reservoir of HIV-1. A mouse monoclonal antibody IgG2a was labelled with 125I and modified using N succinimidyl-3-(2-pyridyldithio)propionate (SPDP) as a heterobifunctional reagent in order to conjugate with liposomes to produce a covalent bond (thioether). SPDP-modified antibody was incubated with liposomes containing 5 mol% of maleimido phenyl butyrate phosphatidylethanolamine (MPB-PE) at room temperature (21 degrees C) for 24 h. L-Ab were separated from free and aggregated antibodies by centrifugation. L-Ab were characterized by measuring particle size and binding to anti-mouse IgG-sepharose. Ninety five per cent of the liposomal (L-Ab) lipid label was bound to anti-mouse IgG-sepharose, whereas only 7% of plain liposomes were bound, indicating non-specific binding. Uptake of L-Ab was measured in human monocyte/macrophages as a function of time and compared with that of plain liposomes. The uptake increased with time and it was 4-6 times greater than that of plain liposomes although part of that effect may have been due to unreacted MPB groups.

Nanocarriers’ entry into the cell: relevance to drug delivery

“…Taking advantage of macrophage receptors to enhance phagocytosis has been further achieved by coupling specific ligands to nanocarriers. For example, grafting rabbit Ig [47] as well as mouse monoclonal antibody [48] to liposomes greatly enhanced their uptake by rat and human macrophages, respectively, most probably through increased FcR binding. Mannose receptors have also been exploited by the introduction of mannose residue and neoglycoprotein on the liposome surface, enhancing uptake by murine Kupffer cells and peritoneal macrophages [49].…”

Novel PEGylated Nanoassemblies Made of Self‐Assembled Squalenoyl Nucleoside Analogues

“…The combined organic extracts were washed with brine, dried over MgSO 4 and concentrated in vacuo. The crude residue was triturated with Et 2 O, the solid was filtered over a sintered glass funnel, and washed with dried ether to give trisnorsqualene-PEG as a white amorphous solid (1.09 g, 62%).…”

“…[2] Therefore, the use of novel injectable nanoparticulate drug delivery systems would be of high interest to circumvent these inconveniences, to protect ddC against degradation, to avoid the rapid blood elimination, and thus to treat HIV infection more effectively. For example, ddCloaded liposomes have been elaborated [4,5] but encapsulation efficiencies of about 26% were obtained with liposomes of 300 nm in diameter corresponding to loadings of only 4.5 mg drug per mmol of total lipids. [5] Additionally, these liposomes suffered from too quick of a release of the encapsulated hydrophilic drug.…”

Role of targeting nanoparticles for cancer immunotherapy and imaging

“…The func tionalized nanoparticles significantly enhanced the expression of CD40 and cytokine production of cytokines IL-1β, IL-6 and TNF-α by alveolar macrophages [37] . Liposomes are mostly used for various drug delivery to macrophage, ligands such as antibody L-Ab is able to modify liposomes for delivery of various materials such as dideoxycytidine triphosphate (ddCTP) to human macrophages via Fc receptor mediated pathway [38] . These systems may be used as antigen carriers or adjuvants for macrophagerelated tumor vaccine.…”