Preparation and Tumor Cell Uptake of Poly(N-isopropylacrylamide) Folate Conjugates

Abstract

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.

Thermosensitive Micelles Based on Folate‐Conjugated Poly(N‐vinylcaprolactam)‐block‐Poly(ethylene glycol) for Tumor‐Targeted Drug Delivery

“…The carbodiimide-activated FA can couple with 2-aminoethanethiol either via a or g carboxyl group of the glutamate residue therefore, a suitable reaction condition was selected to favor linkage of the distal g carboxyl group. [28] Due to the steric hindrance constraints imposed by the FA chain, the folate derivatives were expected to consist mostly of the g-linked isomer. Coupling of thiol with the maleimide group is an efficient preparation method for conjugating FA-SH onto PNVCL-b-PEG-Mal, as the reaction is highly site-specific and convenient to control, and the reaction with thiol moiety generates a stable 3-thiosuccinimidyl ether linkage.…”

Biotin-conjugated block copolymeric nanoparticles as tumor-targeted drug delivery systems

“…The TNBS assay was used to determine quantitatively the conjugation of biotin molecules with PEG, using a previously reported method. 24,36 In addition, the average particle size and size distribution of the nanoparticles were determined using a Zetasizer (Malvern-zetasizer 3000 hs, Malvern, UK) at 25 o C. The morphology of biotin-conjugated PEG/PCL nanoparticles was investigated using a field emission scanning electron microscope (SEM, JEOL-6430F, Kyoto, Japan) at an operating voltage of 10 kV.…”

Size-controlled synthesis of monodisperse core/shell nanogels

“…Nanogel core/shell particles were conjugated with folic acid by a method previously described by Dube et al 40 The core/shell nanogel solution was freeze-dried and then resuspended in 40 mL of 10 mM phosphate buffer pH 4.7. A 2:1 molar ratio of folic acid to amine in the shell was dissolved in 1 mL DMSO.…”