Raman spectroscopy of pH-induced release of zidovudine from lactobionic acid-conjugated PEGylated gold colloids

Abstract

Zidovudine (AZT) adsorbed on colloidal gold nanoparticles (AuNPs) undergoes pH-induced conformational changes according to spectral changes in surface-enhanced Raman scattering (SERS). In acidic pH values conditions, AZT assumes the C(2ʹ)-endo conformer, which binds more weakly to AuNPs than under neutral and alkaline conditions. In this study, density functional theory (DFT) calculations were performed; these calculations also supported the conformation-dependent binding energies. A lactobionic acid-conjugated PEGylated (LA-PEG-SH; molecular weight: 3400) unit was attached to AuNPs to target the asialoglycoprotein receptors overexpressed in hepatocarcinoma cells of Huh7 and SNU-354. The loading efficiency values were measured to be ∼44–49% and ∼66–68% at pH values of 7 and 10, respectively. At an acidic pH of 4.5, they were estimated to be only ∼35–38%. pH-dependent spectral changes were observed for the asymmetric stretching modes of the azide (N[dbnd]N[dbnd]N) bands at 2183 cm−1 (in acidic pH) and at 2129 cm−1 (in basic pH). Cell viability analysis indicated that the LA-PEG-capped, AZT-coated AuNPs specifically inhibited the growth of the targeted hepatocarcinoma cells with better cancer cell killing efficiency than was observed with the LA-PEG-capped AuNPs without AZT. © 2018