DELIVERY OF MACROMOLECULES INTO LIVING CELLS - A METHOD THAT EXPLOITS FOLATE RECEPTOR ENDOCYTOSIS
DELIVERY OF MACROMOLECULES INTO LIVING CELLS - A METHOD THAT EXPLOITS FOLATE RECEPTOR ENDOCYTOSIS
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DOI：
10.1073/pnas.88.13.5572
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发表时间：
1991-07-01
影响因子：
11.1
通讯作者：
LOW, PS
中科院分区：
文献类型：
--
作者：
LEAMON, CP;LOW, PS
大分子进入活细胞的非破坏性传递的困难限制了抗体、基因、酶、多肽和反义寡核苷酸在生物学和医学中的潜在应用。然而，我们发现，如果大分子首先与叶酸共价连接，就可以利用维生素叶酸的自然内吞途径将大分子非破坏性地引入培养细胞。因此，用叶酸连接的核糖核酸酶、辣根过氧化物酶、血清白蛋白、免疫球蛋白或铁蛋白处理KB细胞，可以在2小时内传递10(6)个拷贝的大分子。4-氯-1-萘酚细胞化学染色进一步证明辣根过氧化物酶在内化后保持活性至少6小时。由于叶酸是几乎所有细胞都需要的一种基本维生素，这些观察结果可能为上述许多大分子的科学和医学应用打开了可能性。
Difficulties with the nondestructive delivery of macromolecules into living cells have limited the potential applications of antibodies, genes, enzymes, peptides, and antisense oligonucleotides in biology and medicine. We have found, however, that the natural endocytosis pathway for the vitamin folate can be exploited to nondestructively introduce macromolecules into cultured cells if the macromolecule is first covalently linked to folate. Thus, treatment of KB cells with folate-conjugated ribonuclease, horseradish peroxidase, serum albumin, IgG, or ferritin allowed delivery of > 10(6) copies of the macromolecules within a 2-hr period. Cytochemical staining using 4-chloro-1-naphthol further demonstrated that the horseradish peroxidase retained activity for at least 6 hr after internalization. Since folate is an essential vitamin required in substantial quantities by virtually all cells, these observations may open the possibility of scientific and medical applications for many of the above macromolecules.