Delivery of macromolecules into living cells: a method that exploits folate receptor endocytosis.

TLDR

Difficulties with nondestructive delivery of macromolecules into living cells have limited the potential applications of antibodies, genes, enzymes, peptides, and antisense oligonucleotides, but folate is an essential vitamin required in substantial quantities by virtually all cells, suggesting many scientific and medical applications may be possible. The study aims to exploit the natural endocytosis pathway for folate to nondestructively introduce macromolecules into cultured cells. Macromolecules are covalently conjugated to folate and then internalized via folate receptor‑mediated endocytosis. Treatment of KB cells with folate‑conjugated ribonuclease, horseradish peroxidase, serum albumin, IgG, or ferritin delivered over 10⁶ copies within 2 hours, and cytochemical staining showed that horseradish peroxidase remained active for at least 6 hours after internalization.

Abstract

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 greater than 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.