Preparation and tumor cell uptake of poly(N-isopropylacrylamide) folate conjugates.
Folate conjugates (PNIPAM-NH-FA) of a copolymer of N-isopropylacrylamide (NIPAM) and amino-N'-ethylenedioxy-bis(ethylacrylamide) were prepared by an efficient synthesis leading to random grafting, via a short dioxyethylene spacer, of approximately 7 folic acid residues per macromolecule. The chemical composition of the copolymer was characterized by (1)H NMR and UV/vis spectroscopy. A fluorophore-labeled folate PNIPAM conjugate was tested by in vitro assays performed with cultured KB-31 cells overexpressing the folate receptor. The cellular uptake of the copolymer was found to be temperature dependent and was competitively decreased by free folic acid, indicating that the polymer uptake is mediated specifically by the folate receptor. Hydrophobically modified folate conjugates of NIPAM, amino-N'-ethylenedioxy-bis(ethylacrylamide) copolymers, bearing a small number of n-octadecyl groups were prepared following a modified synthetic procedure for use in future studies of FA-targeted liposomes.
Dubé
Denis
D
Department of Chemistry and Faculty of Pharmacy, Université de Montréal, C. P. 6128, succursale Centre Ville Montréal QC Canada H3C 3J7.
Francis
Mira
M
Leroux
Jean-Christophe
JC
Winnik
Françoise M
FM
D000180:Acrylic Resins / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D005452:Fluoresceins; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007624:KB Cells / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008856:Microscopy, Fluorescence; D009303:Nasopharyngeal Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry; D011956:Receptors, Cell Surface
D000180:Acrylic Resins; D002352:Carrier Proteins; D005452:Fluoresceins; D058973:Folate Receptors, GPI-Anchored; D011108:Polymers; D011956:Receptors, Cell Surface; C039083:5-((4,6-dichloro-1,3,5-triazin-2-yl)amino)fluorescein; C052970:poly-N-isopropylacrylamide; D005492:Folic Acid