Folate-conjugated β-cyclodextrin from click chemistry strategy and for tumor-targeted drug delivery.

To enhance site-specific intracellular delivery against the folate receptor, a drug carrier was designed and synthesized by bioconjugation of folic acid (FA) to β-cyclodextrins (β-CD) through a poly(ethylene glycol) (PEG) spacer from "click chemistry" strategy. The resulted conjugates were confirmed by (1)H NMR and IR spectroscopy. Host-guest interactions between hydrophobic drug and β-CD are capable of entrapping a hydrophobic drug, like 5-Fluorouracil, to form drug-β-CD-PEG-FA nanoparticles (NPs) in aqueous solution. The morphology and size of β-CD-PEG-FA NPs were measured by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The targeting ability of the β-CD-PEG-FA NPs was investigated against two kinds of cell lines (HeLa and A549), which have different amounts of folate receptors on their surface. Confocal image analysis revealed that β-CD-PEG-FA conjugate-assembled nanoparticles exhibited a greater extent of cellular uptake against HeLa cells than A549 cells. This suggests folate-receptor-mediated endocytosis can affect the cellular uptake efficiency of drug-loaded β-CD-PEG-FA NPs. The β-CD-PEG-FA conjugates that are presented may be promising active tumor-targeting carrier candidates via folate mediation.