Copyright © 2018 American Scientific Publishers All rights reserved Printed in the United States of America Article Journal of Biomedical Nanotechnology Vol. 14, 1147–1158, 2018 www.aspbs.com/jbn Inhibition of Al(III)-Induced A 42 Fibrillation and Reduction of Neurotoxicity by Epigallocatechin- 3-Gallate Nanoparticles Neha Atulkumar Singh 1 , Abul Kalam Azad Mandal 2 , and Zaved Ahmed Khan 1 ∗ 1 Department of Integrative Biology, School of Biosciences and Technology, VIT, Vellore 632014, Tamil Nadu, India 2 Department of Biotechnology, School of Biosciences and Technology, VIT, Vellore 632014, Tamil Nadu, India Rational : Accumulation of amyloid beta fibrils is the pathological hallmark of Alzheimer’s disease. Epigallocatechin-3- gallate (EGCG) has shown to possess potent anti-amyloidogenic, metal chelation and antioxidant properties. However, its therapeutic potential is limited in-vivo due to its poor bioavailability and stability. Therefore, the present study aims to evaluate the neuroprotective role of EGCG nanoparticles (nanoEGCG) against Al(III)-induced A 42 fibrillation in-vitro. Method : NanoEGCG was synthesized and its physiochemical characterization was performed. In-vitro release profiles and stability of nanoEGCG in simulated gastro-intestinal fluids, along with its antioxidant and metal chelation potential was evaluated. The anti-amyloidogenic potential of nanoEGCG on A 42 secondary structure and its morphology was evaluated via induction with Al(III) and nanoEGCG treatment. Further, the effect of A 42 on cellular toxicity was also assessed. Result : NanoEGCG with 96% encapsulation efficiency and a hydrodynamic diameter of 300 nm with spherical to slightly ellipsoid shape was synthesized. EGCG release from the nanoparticle occurred in a sustained manner and was stable when released in simulated gastro-intestinal fluids. The antioxidant and metal chelation potential of nanoEGCG over time was better than its free form. Effective inhibition of both A 42 and Al(III) induced A 42 fibrillation with nanoEGCG treatment was noted. This was achieved through the generation of soluble A 42 amorphous aggregates instead of insoluble A 42 oligomers and fibril generation. Significant reduction in cellular toxicity was also noted when treated with nanoEGCG. Conclusion: In conclusion, this study strengthens the hypothesis that EGCG nanoparticles can inhibit Al(III)-induced A 42 fibrillation and its neurotoxicity in-vitro. KEYWORDS: Amyloid Fibrils, Nanoparticles, Alzheimer Disease, Green Tea, Drug Delivery System. BACKGROUND Alzheimer’s disease (AD) imposes a significant economic and social burden, as it is an age-related predominant neurodegenerative disease. Neuropathologically positive lesions such as amyloid plaques, neurofibrillary tangles, cerebral amyloid angiopathy, glial responses and negative lesions such as synaptic loss and neuronal loss character- ize AD. The most important biomarkers for AD pathol- ogy include phosphorylated tau protein (P-tau) and 1–42 amino acid form of beta amyloid (A 42 . 1 Between the two, A 42 fibril accumulation is considered to be the insti- gator of this neurodegenerative pathology and a cascade of ∗ Author to whom correspondence should be addressed. Email: khan.zaved@gmail.com Received: 21 November 2017 Accepted: 17 February 2018 events including neurotoxicity, inflammation and oxidative stress. 2 A 42 fibrillation mainly involves the generation of monomers and dimers that transform into oligomers, protofibrils and fibrils through a multistep nucleated poly- merization process. 3 This alteration in the biophysical prop- erty of the peptide provokes neuronal toxicity. In the presence of metal ions such as Fe(II) and Al(III), this neurotoxicity is notably heightened. 4 The two main fac- tors instigating the acceleration of A 42 fibrillation include defective amyloid precursor protein (APP) proteolysis 5 6 and hindered proteolytic degradation of A 42 peptide. 7 A 42 fibrillation and free metal ions further induce oxida- tive stress via the generation of free radicals through an autocatalytic chain reaction of elements. 8 9 Free metal ion deposition further advances damages and disrupts the func- tioning of various organs. 10 Hence, in addition to the J. Biomed. Nanotechnol. 2018, Vol. 14, No. 6 1550-7033/2018/14/1147/012 doi:10.1166/jbn.2018.2552 1147