Nerve growth factor-carbon nanotube complex exerts prolonged protective effects in an in vitro model of ischemic stroke
The therapeutic potential of nerve growth factor (NGF) against the neurological disorders may be negatively affected by its short half-life. Based on the superior properties of carbon nanotubes (CNTs) for controlled drug delivery, we aimed to prepare CNT-NGF complex and evaluate its effect in an in vitro model of ischemic stroke.Materials and methods:
Multi-walled CNTs (MWCNTs)-NGF complex was prepared using amino-functionalized COOH-MWCNTs and characterized by Fourier transform infrared spectroscopy and transmission electron microscopy. PC12 cells in the absence or presence of NGF (0.5, 1, 2 μg/ml), acid- or amine-modified MWCNTs, or MWCNTs-NGF complex (2, 4, 8 μg/ml) were exposed to 1 and 6 h oxygen-glucose deprivation (OGD) followed by 24 h re-oxygenation. Cytotoxicity and oxidative stress were evaluated.Key findings:
OGD significantly reduced the cell viability (P < 0.001). NGF dose-dependently increased the cell viability only after 1-h OGD (P < 0.05), while, MWCNTs-NGF complex was effective at both 1- and 6-h OGD (P < 0.05, P < 0.001). NGF reduced the formation of condensed nuclei due to 1-h OGD (P < 0.01, P < 0.001), while, MWCNTs-NGF showed efficiency at both time points (P < 0.05, P < 0.01, P < 0.001). OGD significantly increased malondialdehyde (MDA) content and decreased catalase (CAT) and superoxide dismutase (SOD) activities (P < 0.001). After 1-h OGD, NGF reduced MDA (P < 0.001) and increased CAT (P < 0.05, P < 0.01) and SOD (P < 0.01), while, MWCNTs-NGF was effective after both 1- and 6-h OGD (MDA: P < 0.01, P < 0.001, CAT: P < 0.001, SOD: P < 0.01, P < 0.001).Significance:
Aminated MWCNTs-NGF complex by providing longer lasting effects for NGF might be of therapeutic significance against the disorders associated with NGF deficiency.