LDL-mediated targeting of liposomes to leukemic lymphocytes in vitro.

Abstract

Communicated by P.DouzouWe describe a method for the covalent coupling of low-density lipoproteins (LDL) to the surface of small unilameliar vesicles, and the delivery of the liposome content to leukemic L2C Iymphocytes in vitro. We demonstrate the stability of the linkage between LDL and liposomes, the preservation of vesicle integrity and the affmity of the LDL for their specific receptors after the coupling reaction. Hygromycin B, an impermeant inhibitor of protein synthesis, was encapsulated in the targeted liposomes, and delivered into the cytoplasm of leukemic L2C lymphocytes by the LDL pathway, as demonstrated by the lethal effect on cells measured by 51chromium-release assay.

Targeting receptor-mediated endocytotic pathways with nanoparticles: Rationale and advances

“…LDL-mediated targeting of liposomes to leukemic lymphocytes in vitro was reported as early as 1985 [3]. Recently, siRNA delivery by LDL nanoparticles also showed enhanced gene silencing in HepG2 cells compared to their analog without LDL [205].…”

“…TfR remains a major drug delivery target, both in tumors as well as for enabling transcytosis of conjugates across barrier epithelial and endothelial cells. Another early target, the low density lipoprotein receptor (LDLR) has been of continuous interest since the early demonstration of LDL-mediated targeting of liposomes to leukemic lymphocytes in 1985 [3]. However, the repertoire of other prospective receptor targets for internalization of conjugates has significantly increased since this early work.…”

Co-Encapsulating the Fusogenic Peptide INF7 and Molecular Imaging Probes in Liposomes Increases Intracellular Signal and Probe Retention

“…Endocytosis is the principal mode of liposome uptake by cells. Susceptibility of liposomes to endocytosis can be modulated by chemical modification of the liposome—e.g., by modifying the lipid composition or surface charge [ 10 , 11 ], and by decorating the liposome surface with specific polymers [ 2 , 12 , 13 ], ligands [ 14 – 16 ] or antibodies [ 5 , 6 , 17 ]. After endocytosis, liposomes are degraded in the endolysosomal pathway ( Fig.…”

Stealth™ Liposomes for the Targeting of Drugs in Cancer Therapy

“…Transferrin-liposomes loaded with cytosine arabinoside were shown to result in enhanced toxicity against CV -1 cells compared to free drugs (Brown and Silvius 1990). Binding of folate, apo-B or transferrin to their respective receptors results in internalization ofthe liposome and its contents into the target cells, which may result in increased drug delivery to the cells (Vidal et al 1985;Brown and Silvius 1990;Lee and Low 1995;Lee and Huang 1996). Other targeting molecules which could be exploited in the treatment of cancer include nerve growth factor and epidermal growth factor (Rosenberg et al 1987;Ishii et al 1989).…”

“…This receptor can be targeted by attaching apolipoprotein-B (Apo-B) at the liposome surface. Apo-B-liposomes loaded with hydromycin B resulted in selective cytotoxicity to leukemic L2C lymphocytes in vitro (Vidal et al 1985). Likewise, the transferrin receptor is expressed at high densities on some malignant cells.…”