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Targeted killing of cultured cells by receptor-dependent photosensitization.

This paper describes a method, designated "receptor-dependent photosensitization," by which the receptor-mediated endocytosis of low density lipoprotein (LDL) can be used to deliver a photosensitizing agent, pyrene, to cultured human and animal cells. The hydrophobic core of LDL is extracted and replaced with pyrene covalently coupled to cholesteryl oleate. This reconstituted LDL enters cells in significant amounts only when the cells express LDL receptors, resulting in the accumulation of pyrene cholesteryl oleate within lysosomes. Subsequent exposure of the cells to ultraviolet light leads to cell death. Cells killed by this technique include normal and simian virus 40-transformed human fibroblasts, human A-431 epidermal carcinoma cells, Chinese hamster ovary cells, and mouse L cells, all of which express LDL receptors. Mutant fibroblasts from a patient with homozygous familial hypercholesterolemia, which lack LDL receptors, do not take up significant amounts of the pyrene-containing LDL and are not killed by subsequent exposure to light. The current experiments establish the feasibility of receptor-dependent photosensitization as an efficient and selective method for killing cultured human and animal cells.