Abstract
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 cholsteryl 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5717-5721 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 78 |
| Issue number | 9 II |
| State | Published - 1981 |
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ASJC Scopus subject areas
- Genetics
- General
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Targeted killing of cultured cells by receptor-dependent photosensitization. / Mosley, S. T.; Goldstein, Joseph L; Brown, Michael S; Falck, J R; Anderson, R. G.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 78, No. 9 II, 1981, p. 5717-5721.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Targeted killing of cultured cells by receptor-dependent photosensitization
AU - Mosley, S. T.
AU - Goldstein, Joseph L
AU - Brown, Michael S
AU - Falck, J R
AU - Anderson, R. G.
PY - 1981
Y1 - 1981
N2 - 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 cholsteryl 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.
AB - 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 cholsteryl 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.
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M3 - Article
C2 - 6272315
AN - SCOPUS:0001533946
VL - 78
SP - 5717
EP - 5721
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 9 II
ER -