Synthesis and in vitro biological evaluation as antitumour drug carriers of folate-targeted N-isopropylacrylamide-based nanohydrogels

摘要

Copolymeric nanohydrogels based on N-isopropylacrylamide, N-(pyridin-4-ylmethyl)acrylamide and tert-butyl-2-acrylamidoethyl carbamate, synthesized by microemulsion polymerization, were characterized using Fourier transform infrared spectroscopy and their size (38-52 nm) determined using quasielastic light scattering. Folic acid was covalently attached to the nanohydrogels (1.40 ± 0.07 mmol g~(-1)). Tamoxifen (6.7 ± 0.2-7.3 ± 1.2 μg TMX mg~(-1) nanohydrogel), a hydrophobic anticancer drug, and 5-fluorouracil (7.7 ± 0.7-10.14 ± 1.75 μg 5-FU mg~(-1) nanohydrogel), a hydrophilic anticancer drug, were loaded into the nanohydrogels. Maximum in vitro TMX release (77-84% of loaded drug) depended on interactions of the drug with hydrophobic clusters of the nanogels; however, no nanogel/5-FU interactions allowed total release of the loaded drug. The cytotoxicity of unloaded nanohydrogels in MCF7, T47D and HeLa cells was low. Cell uptake of nanogels without bound folic acid took place in the three cell types by unspecific internalization in a time-dependent process. Cell uptake increased for folic acid-targeted nanohydrogels in T47D and HeLa cells, which have folate receptors. The administration of 10 and 30 μmol L~(-1) TMX by TMX-loaded nanogels and 10 μmol L~(-1) 5-FU by 5-FU-loaded nanogels was effective on the three cell types, and the best results were obtained for folic acid-targeted nanohydrogels.