Modulating protein amyloid aggregation with nanomaterials

Abstract

Direct exposure or intake of nanopaticles (NPs) to the human body can invoke a series of biological responses, some of which are deleterious, and as such the role of NPs in vivo requires thorough examination. Over the past decade, it has been established that biomolecules such as proteins can bind NPs to form a ‘corona’, where the structures and dynamics of NP-associated proteins can assign new functionality, systemic distribution and toxicity. However, the behavior and fate of NPs in biological systems are still far from being fully understood. Growing evidence has shown that some natural or artificial NPs could either up- or down-regulate protein amyloid aggregation, which is associated with neurodegenerative diseases like Alzheimer’s and Parkinson’s diseases, as well as metabolic diseases such as type 2 diabetes. These effects can be either indirect (e.g., through a crowding effect) or direct, depending on the NP composition, size, shape and surface chemistry. However, efforts to design anti-amyloid NPs for biomedical applications have been largely hindered by insufficient understanding of the complex processes, even though proof-of-concept experiments have been conducted. Therefore, exploring the general mechanisms of NP-meditated protein aggregation marks an emerging field in bio-nano research and a new stage of handling nanotechnology that not only aids in elucidating the origin of nanotoxicity, but also provides a foundation for engineering de novo anti-amyloid nanomedicines. In this review, we summarize research on NP-mediated protein amyloid aggregation, with the goal of contributing to sustained nanotechnology and safe nanomedicine against amyloid diseases.

Lab-On-A-Chip for the Development of Pro-/Anti-Angiogenic Nanomedicines to Treat Brain Diseases

“…There are a couple of shortcomings regarding the use of NPs to treat brain-related conditions. For example, NPs have been found to induce amyloidogenicity [104], and, for this reason, it is important in the future to characterize their complex dynamic surface properties.…”

Insights into Characterization Methods and Biomedical Applications of Nanoparticle–Protein Corona

“…( b ) The kinetic process of protein amyloid fibrillization. Reproduced by permission from The Royal Society of Chemistry [ 181 ] with minor modification.…”

The Enigma of Amyloid Forming Proteins: Insights From Molecular Simulations

“…[63] Several reviews summarise the plethora of research describing the common modes in which nanostructured materials interact with biological molecules such as membranes, DNA, and peptides/proteins, and, within our current focus, their possible role in protein aggregation. [64][65][66][67][68] Despite the extensive number of studies in this field there is still a lot to learn about nanomaterial interactions with biological matter. Specifically in relation to amyloid formation, nanomaterials may inhibit or promote cytotoxicity at three different stages of the fibrillation process: (1) by disruption of the nucleation phase, i.e.…”

“…Factors such as shape, size, and surface chemistry, including concentration and composition of surface functionalisation (and charge), have been shown to impact the ability of nanoparticles to inhibit or promote aggregation. Considerable research has been undertaken recently to explore how these factors specifically affect fibril formation ( [64][65][66][67] and references therein).…”