Chemical modification of ligands for cell receptors to introduce foreign compounds into the cells

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Abstract

PURPOSE:

In all forms of drug therapy, clinicians must ensure that the maximum therapeutic benefit is achieved without inducing unacceptable toxicity. An improvement in the therapeutic index could be achieved through the targeting of drugs selectively to cancer cells.

METHODS:

We have developed a delivery system that uses receptormediated endocytosis to introduce oligodeoxynucleotides into cells bearing receptors for the ligands used as a vehicle. Human transferrin, as well as folic acid and steroid, has been covalently linked to polylysines of various sizes through a disulfite bridge and used as oligomer carriers.

RESULTS AND DISCUSSION:

The inhibitory effect of c-mybantisense oligodeoxynucleotides conjugate to modified transferrin on LoVo Dx cell proliferation was examined. Protocols to modify physiologic ligands to be used as vehicles for a selective delivery are shown. Modified ligand molecules should also be used to covalently bind liposome-carrying compounds able to affect neoplastic growth.

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