[Targeting of tumor cells by low density lipoproteins: principle and use of ellipticin derivatives].

Cells acquire cholesterol via de novo synthesis and high affinity receptor-mediated uptake of low-density lipoprotein (LDL). Some tumor tissues display increased receptor-mediated uptake of LDL as compared with the corresponding normal tissues. This increased LDL receptor activity is unexplained: a high cholesterol demand for cell growth or a mechanism directly linked to cell transformation. LDL has therefore been proposed as a potential carrier for chemotherapeutic agents. Various methods have been used to incorporate antineoplastic lipophilic drugs into LDL. The resultant drug-LDL complexes have been shown to be cytotoxic towards tumor cells in vitro, via the LDL receptor dependent pathway. However little is now on the in vivo fate of this complex. We described the incorporation of lipophilic derivatives of ellipticine into LDL by a fusion or facilitated transfer technique between drug containing microemulsions and LDL. The drug-LDL complex expressed similar metabolic activity, in vitro and in vivo, than native LDL. Initial experiments with melanoma B16 tumor-bearing mice suggest that LDL may be a potential drug carrier in the treatment of malignant diseases. The knowledge of the molecular mechanism of the expression of the LDL receptor in tumor cells and the ability to downregulate the LDL receptor in the normal tissues, will define the application field of this targeting approach.