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 β-amyloid (Aβ)(25-35)-induced toxicity toward Neuro-2A cells. PEG-C(60)-3 and PTX-C(60)-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-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 Aβ 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 Aβ-associated diseases.


BACKGROUND
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.
Lee
Chi-Ming
CM
Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
Huang
Sheng-Tung
ST
Huang
Shih-Hao
SH
Lin
Hui-Wen
HW
Tsai
Hsiang-Ping
HP
Wu
Jui-Yu
JY
Lin
Chun-Mao
CM
Chen
Chien-Tsu
CT
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D037741:Fullerenes / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008854:Microscopy, Electron; D053758:Nanoparticles / Q000737:chemistry*; D010431:Pentoxifylline / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D016229:Amyloid beta-Peptides; D037741:Fullerenes; D017382:Reactive Oxygen Species; C069837:fullerene C60; D010431:Pentoxifylline