Nerve growth factor-carbon nanotube complex exerts prolonged protective effects in an in vitro model of ischemic stroke

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Abstract

Aims:

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.

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