Low density lipoprotein for cytotoxic drug targeting: improved activity of elliptinium derivative against B16 melanoma in mice.

Abstract	Significant low density lipoprotein (LDL) uptake by tumour cells led to the use of LDL as a discriminatory vehicle for the delivery of cytotoxic drugs. In the current study, the lipophilic elliptinium derivative, elliptinium-oleate (OL-NME), was incorporated into LDL to reach an incorporation level of 400 molecules per LDL particle. The OL-NME-LDL complex showed cytotoxic effects on normal human fibroblasts while the cytotoxicity was not observed on receptor-defective human fibroblasts, indicating the ability of the complex to be preferentially metabolised by the LDL receptor. In vivo metabolism of the complex was related to the LDL receptor pathway. The metabolic clearance was the same for native LDL (17.1 ml h-1) and OL-NME-LDL complex (16.2 ml h-1). LDL incorporated OL-NME enhanced the anti-tumour activity against murine B16 melanoma model; this resulted from increased efficacy for OL-NME-LDL at doses equal to free 9-OH-NME (157 vs 76 of Increase Life Span (ILS) (%) values after intraperitoneal (i.p.) drug injection on i.p. implanted tumour model and 45 vs -2 ILS (%) values after intravenous drug injection on subcutaneous implanted tumour model). These data suggest that LDL improves the potency of lipophilic cytotoxic drugs against tumours that express LDL receptor activity.
Authors	M Samadi-Baboli, G Favre, P Canal, G Soula
Journal	British journal of cancer (Br J Cancer) Vol. 68 Issue 2 Pg. 319-26 (Aug 1993) ISSN: 0007-0920 [Print] England
PMID	8347487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	9-oleyloxy-N(2)-methylellipticinium oleate Drug Carriers Ellipticines Emulsions Iodine Radioisotopes Lipoproteins, LDL Receptors, LDL elliptinium Serum Albumin, Bovine
Topics	Animals Cells, Cultured (cytology, drug effects) Drug Carriers Drug Stability Ellipticines (administration & dosage, therapeutic use, toxicity) Emulsions Humans Iodine Radioisotopes Lipoproteins, LDL (blood, pharmacokinetics) Male Melanoma, Experimental (drug therapy) Metabolic Clearance Rate Mice Mice, Inbred BALB C Rabbits Receptors, LDL (metabolism) Serum Albumin, Bovine Skin (cytology, drug effects)

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