title: Differential effects of silver and iron oxide nanoparticles on IAPP amyloid aggregation.
abstract: Recent studies have shown promise on the use of small molecules and nanoparticles (NPs) for the inhibition of protein aggregation, a hallmark of neurodegenerative diseases and type 2 diabetes (T2D). Towards this end here we show the differential effects of silver and iron oxide nanoparticles (AgNPs and IONPs) on the mesoscopic properties of human islet amyloid polypeptide (IAPP) aggregation associated with T2D. Both citrate- and branched polyethyleneimine-coated AgNPs (c-AgNPs, bPEI-AgNPs) inhibited IAPP aggregation at 500 μg mL-1, likely through electrostatic attraction and sequestering of IAPP monomers from fibrillation. In comparison, bare, brushed polyethylene glycol- and phosphorylcholine-grafted IONPs (bPEG-IONPs, bPC-IONPs) at 500 μg mL-1elicited no major effect on IAPP fibril contour length, while bPC-IONPs induced significant fibril softening and looping likely mediated by dipolar interactions. While monovalent Ag+up to 50 μg mL-1showed no effect on the contour length or stiffness of IAPP fibrils, multivalent Fe3+at 5 μg mL-1halted IAPP fibrillation likely through ion-peptide crosslinking. Except bPEI-AgNPs, all three types of IONPs and c-AgNPs at 100 μg mL-1alleviated IAPP toxicity in HEK293 cells indicating no clear correlation between protein aggregation and their induced cytotoxicity. This study demonstrates the complexity of protein aggregation intervened by NPs of different physicochemical properties and - together with existing literature - facilitates nanotechnological applications for mitigating amyloid-mediated pathologies.
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia. thomas.p.davis@monash.edu pu-chun.ke@monash.edu.
authors.forename: Miaoyi
authors.identifier: http://orcid.org/0000-0002-6064-9114
authors.initials: M
authors.lastname: Wang
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia. thomas.p.davis@monash.edu pu-chun.ke@monash.edu.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Kakinen
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia. thomas.p.davis@monash.edu pu-chun.ke@monash.edu.
authors.forename: Emily H
authors.initials: EH
authors.lastname: Pilkington
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia. thomas.p.davis@monash.edu pu-chun.ke@monash.edu and Department of Chemistry, Warwick University, Gibbet Hill, Coventry, CV4 7AL, UK.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Davis
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia. thomas.p.davis@monash.edu pu-chun.ke@monash.edu.
authors.forename: Pu Chun
authors.identifier: http://orcid.org/0000-0003-2134-0859
authors.initials: PC
authors.lastname: Ke
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D053758:Nanoparticles / Q000737:chemistry; D066329:Protein Aggregates / Q000187:drug effects*; D012834:Silver / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000682:Amyloid; D005290:Ferric Compounds; D058228:Islet Amyloid Polypeptide; D066329:Protein Aggregates; C000499:ferric oxide; D012834:Silver