β-Cyclodextrin Reverses Binding of Perfluorooctanoic Acid to Human Serum Albumin

Perfluorooctanoic acid (PFOA), a persistent organic pollutant known to cause adverse health effects, strongly binds to human serum albumin (HSA). β-Cyclodextrin (β-CD), a nontoxic cyclic sugar, strongly complexes PFOA in a host-guest complex and has been proposed for environmental remediation of PFOA. The interactions between HSA, PFOA, and β-CD were investigated in order to determine if β-CD can reverse the binding of PFOA to HSA, with potential therapeutic applications toward exposure to PFOA. ¹⁹F Nuclear magnetic resonance (NMR), circular dichroism, and fluorescence spectroscopies were used to study these interactions. Multiple PFOA binding sites to HSA, one with strong affinity and others with low affinity, are evident from changes in the fluorescence emission spectra of HSA and the fluorescence lifetimes of the single Trp residue in HSA with increasing PFOA concentration. Structural changes in the protein are also evident from changes in the circular dichroism spectra of HSA upon titration of PFOA. Addition of β-CD to PFOA and HSA reversed these changes, indicating that formation of the β-CD:PFOA host-guest complex is favored even in the presence of HSA. Equimolar β-CD to PFOA (1:1 β-CD:PFOA ratio) causes dissociation of the weakly bound PFOA from HSA, whereas excess β-CD relative to PFOA (5:1 β-CD:PFOA ratio) leads to the complete disassociation of the strongly bound PFOA molecule from HSA. The ¹⁹F NMR studies further suggest that the 2:1 β-CD:PFOA complex inhibits PFOA binding to HSA. These data demonstrate that β-CD has potential to be used in therapeutic applications for PFOA in human blood.