Low-density lipoprotein receptor-mediated delivery of a lipophilic daunorubicin derivative to B16 tumours in mice using apolipoprotein E-enriched liposomes

Abstract

Summary Many tumours express relatively high levels of low-density lipoprotein (LDL) receptors on their membranes. The LDL receptor is, therefore, an attractive target for the selective delivery of antineoplastic drugs to tumour cells. We reported previously on the synthesis of small apolipoprotein E (apoE)-containing liposomes that behave in vivo in a very similar way to native LDL. In this study, we (LAD). Tissue distribution studies showed that LAD-loaded apoE liposomes were taken up and processed by the major LDL receptor-expressing organs (i.e. adrenals, liver and spleen). Of all other tissues, the tumour showed the highest uptake. The distribution pattems of LAD-loaded apoE liposomes and native LDL in the tumour-bearing mice were very similar, which supports the role of the LDL receptor in the disposition of the prodrug-loaded particles. The disposition of LAD followed the pattem of the liposomal carrier. We conclude that apoE liposomes enable LDL receptor-mediated specific delivery of antineoplastic (pro)

Mr and fluorescent imaging of low-density lipoprotein receptors1

“…This suggests that in normal liver the labeled LDL was primarily taken up via LDLR-mediated endocytosis whereas the uptake via nonspecific endocytosis is rather low as demonstrated in the LDLrϪ/ Ϫliver, which has no LDLR on hepatocytes as the result of LDLr gene knockout (36). The 30% T 1 shortening observed in B16 melanoma after injection of PTIR267-labeled LDL suggests that LDLR density in B16 tumor may not be as high as in the normal liver, and is consistent with previous reports (15).…”

“…In contrast, such regulation is absent in tumors expressing LDLR (8,9). Therefore, differential uptake by tumors can be achieved, and that provides the basis for delivery of various lipophilic antineoplastic agents as LDL conjugates (15)(16)(17)(18).…”

Determination of the Upper Size Limit for Uptake and Processing of Ligands by the Asialoglycoprotein Receptor on Hepatocytesin Vitro and in Vivo

“…This affinity is similar to that of the triantennary glycopeptides YEE(GalNAcAH) 3 and YDD(G-ah-GalNAc) 3 that have been developed by Lee and Lee (37,38) and utilized for ASGPr-directed delivery of DNA (54) and oligodeoxynucleoside methylphosphonates (55). To establish firm association with liposomes, the glycoside was coupled to lithocholic oleate, which has already been shown to confer a stable incorporation of antisense oligodeoxynucleotides (36), anthracyclines (56), and glycosides (32) into lipidic particles. Also in this study, a tight association of the Gal 3 and GalNAc 3 -terminated glycolipids with the liposomes was observed, withstanding dissociation in the blood.…”

Trojan Horse Meets Magic Bullet to Spawn a Novel, Highly Effective Drug Delivery Model

“…Additionally, hydrophobic derivatives of drugs may be prepared to make them appropriate core components for incorporation into the lipoproteins [16][17][18][19] to expand the scope of the rHDL drug delivery system.…”