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

Lee, Chi-Ming; Huang, Sheng-Tung; Huang, Shih-Hao; Lin, Hui-Wen; Tsai, Hsiang-Ping; Wu, Jui-Yu; Lin, Chun-Mao; Chen, Chien-Tsu

doi:10.1016/j.nano.2010.06.009

« Previous Next »Nanomedicine: Nanotechnology, Biology and Medicine
Volume 7, Issue 1 , Pages 107-114, February 2011

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

Chi-Ming Lee, MS
- Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
- Instrument Center, Taipei Medical University, Taipei, Taiwan
- These two authors contributed equally to this work.
Sheng-Tung Huang, PhD
- Institute of Biotechnology, National Taipei University of Technology, Taipei, Taiwan
- These two authors contributed equally to this work.
Shih-Hao Huang, PhD
- Department of Food Science, Taipei College of Maritime Technology, Taipei, Taiwan
Hui-Wen Lin, PhD
- Biostatistic Research and Consulting Center, Taipei Medical University, Taipei, Taiwan
Hsiang-Ping Tsai, MS
- Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
- School of Medicine, Taipei Medical University, Taipei, Taiwan
Jui-Yu Wu, PhD
- School of Medicine, Taipei Medical University, Taipei, Taiwan
Chun-Mao Lin, PhD
- School of Medicine, Taipei Medical University, Taipei, Taiwan
- Orthopedics Research Center, Taipei Medical University Hospital, Taipei, Taiwan
- Corresponding author: School of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Chien-Tsu Chen, PhD
- School of Medicine, Taipei Medical University, Taipei, Taiwan

Received 2 February 2010; accepted 26 June 2010. published online 09 July 2010.

Abstract

Many studies have focused on the neuroprotective effects of C₆₀ fullerene-derived nanomaterials. The peculiar structure of C₆₀ 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-C₆₀-3, a C₆₀ fullerene derivative incorporating poly(ethylene glycol), and its pentoxifylline-bearing hybrid (PTX-C₆₀-2) were investigated against β-amyloid (Aβ)_25-35-induced toxicity toward Neuro-2A cells. PEG-C₆₀-3 and PTX-C₆₀-2 significantly reduced Aβ_25-35-induced cytotoxicity, with comparable activities in decreasing reactive oxygen species and maintaining the mitochondrial membrane potential. Aβ_25-35 treatment elicited adenosine monophosphate-activated protein kinase–associated autophagy. Cytoprotection by PEG-C₆₀-3 and PTX-C₆₀-2 was partially diminished by an autophagy inhibitor, indicating that the elicited autophagy and antioxidative activities protect cells from Aβ damage. PTX-C₆₀-2 was more effective than PEG-C₆₀-3 at enduring the induced autophagy. Our results offer new insights into therapeutic drug design using C₆₀ fullerene–PTX dyad nanoparticles against Aβ-associated diseases.

From the Clinical Editor

The neuroprotective effects of C60 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.

Graphical Abstract

The structure of the C₆₀ fulleropyrrolidine-xanthine hybrid particle (Figure 1).