C60 fullerene-pentoxifylline dyad nanoparticles enhance autophagy to avoid cytotoxic effects caused by the β-amyloid peptide

Many studies have focused on the neuroprotective effects of C-60 fullerene-derived nanomaterials. The peculiar structure of C-60 fullerene, which is capable of adding multiple radicals per molecule, serves as a radical sponge, and it can be an effective antioxidant by reducing cytotoxic effects caused by intracellular oxidative stress. In this study, PEG-C-60-3, a C-60 fullerene derivative incorporating poly(ethylene glycol), and its pentoxifylline-bearing hybrid (PTX-C-60-2) were investigated against beta-amyloid (A beta)(25-35)-induced toxicity toward Neuro-2A cells. PEG-C-60-3 and PTX-C-60-2 significantly reduced A beta(25-35)-induced cytotoxicity, with comparable activities in decreasing reactive oxygen species and maintaining the mitochondrial membrane potential. A beta(25-35) treatment elicited adenosine monophosphate-activated protein kinase-associated autophagy. Cytoprotection by PEG-C-60-3 and PTX-C-60-2 was partially diminished by an autophagy inhibitor, indicating that the elicited autophagy and antioxidative activities protect cells from A beta damage. PTX-C-60-2 was more effective than PEG-C-60-3 at enduring the induced autophagy. Our results offer new insights into therapeutic drug design using C-60 fullerene-PTX dyad nanoparticles against A beta-associated diseases. From the Clinical Editor: The neuroprotective effects of C-60 fullerene-derived nanomaterials are known and thought to be related to their capacity of absorbing multiple free radicals. In this study, another interesting property is presented: they may enhance autophagy of beta-amyloid peptide, which could minimize the damaging effects of this peptide. (C) 2011 Elsevier Inc. All rights reserved.