Nanoplastic Stimulates the Amyloidogenesis of Parkinson's Alpha-Synuclein NACore.

Environmental plastic wastes are potential health hazards due to their prevalence as well as their versatility in initiating physical, chemical, and biological interactions and transformations. Indeed, recent research has implicated the adverse effects of micro- and nano-plastics, including their neurotoxicity, yet how plastic particulates may impact the aggregation pathway and toxicity of amyloid proteins pertinent to the pathologies of neurological diseases remains unknown. Here, electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) is employed to reveal the polymorphic oligomerization of NACore, a surrogate of alpha-synuclein that is associated with the pathogenesis of Parkinson's disease. These data indicate that the production rate and population of the NACore oligomers are modulated by their exposure to a polystyrene nanoplastic, and these cellular assays further reveal an elevated NACore toxicity in microglial cells elicited by the nanoplastic. These simulations confirm that the nanoplastic-NACore association is promoted by their hydrophobic interactions. These findings are corroborated by an impairment in zebrafish hatching, survival, and development in vivo upon their embryonic exposure to the nanoplastic. Together, this study has uncovered the dynamics and mechanism of amyloidogenesis elevated by a nanoplastic trigger, shedding a new light on the neurological burden of plastic pollution.

Plasma Proteome Association and Catalytic Activity of Stealth Polymer-Grafted Iron Oxide Nanoparticles.

Polyethylene glycol (PEG) is widely used as an antifouling and stealth polymer in surface engineering and nanomedicine. However, recent research has revealed adverse effects of bioaccumulation and immunogenicity following the administration of PEG, prompting this proteomic examination of the plasma protein coronae association with superparamagnetic iron oxide nanoparticles (IONPs) grafted with brushed PEG (bPEG) and an alternative, brushed phosphorylcholine (bPC). Using label-free quantitation by liquid chromatography tandem-mass spectrometry, this study determines protein abundances for the in vitro hard coronae of bare, bPC-, and bPEG-grafted IONPs in human plasma. This study also shows unique protein compositions in the plasma coronae of each IONP, including enrichment of coagulation factors and immunogenic complement proteins with bPEG, and enhanced binding of apolipoproteins with bPC. Functional analysis reveals that plasma protein coronae elevate the horseradish peroxidase-like activities of the bPC- and bPEG-IONPs by approximately twofold, an effect likely mediated by the diverse composition and physicochemical properties of the polymers as well as their associated plasma proteins. Taken together, these observations support the rational design of stealth polymers based on a quantitative understanding of the interplay between IONPs and the plasma proteome, and should prove beneficial for the development of materials for nanomedicine, biosensing, and catalysis.

Star Polymers Reduce Islet Amyloid Polypeptide Toxicity via Accelerated Amyloid Aggregation.

Protein aggregation into amyloid fibrils is a ubiquitous phenomenon across the spectrum of neurodegenerative disorders and type 2 diabetes. A common strategy against amyloidogenesis is to minimize the populations of toxic oligomers and protofibrils by inhibiting protein aggregation with small molecules or nanoparticles. However, melanin synthesis in nature is realized by accelerated protein fibrillation to circumvent accumulation of toxic intermediates. Accordingly, we designed and demonstrated the use of star-shaped poly(2-hydroxyethyl acrylate) (PHEA) nanostructures for promoting aggregation while ameliorating the toxicity of human islet amyloid polypeptide (IAPP), the peptide involved in glycemic control and the pathology of type 2 diabetes. The binding of PHEA elevated the ß-sheet content in IAPP aggregates while rendering a new morphology of "stelliform" amyloids originating from the polymers. Atomistic molecular dynamics simulations revealed that the PHEA arms served as rodlike scaffolds for IAPP binding and subsequently accelerated IAPP aggregation by increased local peptide concentration. The tertiary structure of the star nanoparticles was found to be essential for driving the specific interactions required to impel the accelerated IAPP aggregation. This study sheds new light on the structure-toxicity relationship of IAPP and points to the potential of exploiting star polymers as a new class of therapeutic agents against amyloidogenesis.

Comparison of nanotube-protein corona composition in cell culture media.

In biological environments, nanomaterials associate with proteins forming a protein corona (PC). The PC may alter the nanomaterial's pharmacokinetics and pharmacodynamics, thereby influencing toxicity. Using a label-free mass spectrometry-based proteomics approach, the composition of the PC is examined for a set of nanotubes (NTs) including unmodified and carboxylated single- (SWCNT) and multi-walled carbon nanotubes (MWCNT), polyvinylpyrrolidone (PVP)-coated MWCNT (MWCNT-PVP), and nanoclay. NTs are incubated for 1 h in simulated cell culture conditions, then washed, resuspended in PBS, and assessed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for their associated PC. To determine those attributes that influence PC formation, the NTs are extensively characterized. NTs had negative zeta potentials in water (SWCNT-COOH < MWCNT-COOH < unmodified NTs) while carboxylation increases their hydrodynamic sizes. All NTs are also found to associate a common subset of proteins including albumin, titin, and apolipoproteins. SWCNT-COOH and MWCNT-COOH are found to bind the greatest number of proteins (181 and 133 respectively) compared to unmodified NTs (<100), suggesting covalent binding to protein amines. Modified NTs bind a number of unique proteins compared to unmodified NTs, implying hydrogen bonding and electrostatic interactions are involved in PC formation. PVP-coating of MWCNT did not influence PC composition, further reinforcing the possibility of hydrogen bonding and electrostatic interactions. No relationships are found between PC composition and corresponding isoelectric point, hydropathy, or aliphatic index, implying minimal roles of hydrophobic interaction and pi-stacking.

Exploiting the physicochemical properties of dendritic polymers for environmental and biological applications.

In this perspective we first examine the rich physicochemical properties of dendritic polymers for hosting cations, anions, and polyaromatic hydrocarbons. We then extrapolate these conceptual discussions to the use of dendritic polymers in humic acid antifouling, oil dispersion, copper sensing, and fullerenol remediation. In addition, we review the state-of-the-art of dendrimer research and elaborate on its implications for water purification, environmental remediation, nanomedicine, and energy harvesting.

Anionic nanoplastic exposure induces endothelial leakiness.

The global-scale production of plastics has been instrumental in advancing modern society, while the rising accumulation of plastics in landfills, oceans, and anything in between has become a major stressor on environmental sustainability, climate, and, potentially, human health. While mechanical and chemical forces of man and nature can eventually break down or recycle plastics, our understanding of the biological fingerprints of plastics, especially of nanoplastics, remains poor. Here we report on a phenomenon associated with the nanoplastic forms of anionic polystyrene and poly(methyl methacrylate), where their introduction disrupted the vascular endothelial cadherin junctions in a dose-dependent manner, as revealed by confocal fluorescence microscopy, signaling pathways, molecular dynamics simulations, as well as ex vivo and in vivo assays with animal model systems. Collectively, our results implicated nanoplastics-induced vasculature permeability as primarily biophysical-biochemical in nature, uncorrelated with cytotoxic events such as reactive oxygen species production, autophagy, and apoptosis. This uncovered route of paracellular transport has opened up vast avenues for investigating the behaviour and biological effects of nanoplastics, which may offer crucial insights for guiding innovations towards a sustainable plastics industry and environmental remediation.

Probing the Aggregation and Immune Response of Human Islet Amyloid Polypeptides with Ligand-Stabilized Gold Nanoparticles.

The use of nanomaterials has recently become an emerging strategy against protein amyloidosis associated with a range of metabolic and brain diseases. To facilitate research in this area, here we first demonstrated the use of hyperspectral imaging (HSI) and COMSOL simulations for reporting the aggregation of human islet amyloid polypeptides (IAPPs), a hallmark of type 2 diabetes, as well as the physical interactions between the peptide and gold nanoparticles (AuNPs) grafted with citrate and poly(ethylene glycol) (PEG400 and PEG3000). We found a distinct anticorrelation between increased IAPP aggregation and decreased spectral red shifts incurred in the AuNP plasmonic resonance. Moreover, Jurkat cells exposed to IAPP and AuNPs were characterized by quantifying their cytokine secretions with a localized surface plasmon resonance (LSPR) immunoassay, where a peak response was registered for the most toxic IAPP oligomers and most suppressed by citrate-coated AuNPs. This study demonstrated the potential of using HSI and LSPR as two new platforms for the facile examination of protein aggregation and their induced immune response associated with amyloid diseases.

Uptake and transcytosis of functionalized superparamagnetic iron oxide nanoparticles in an in vitro blood brain barrier model.

Two major hurdles in nanomedicine are the limited strategies for synthesizing stealth nanoparticles and the poor efficacy of the nanoparticles in translocating across the blood brain barrier (BBB). Here we examined the uptake and transcytosis of iron oxide nanoparticles (IONPs) grafted with biomimetic phosphorylcholine (PC) brushes in an in vitro BBB model system, and compared them with bare, PEG or PC-PEG mixture grafted IONPs. Hyperspectral imaging indicated IONP co-localization with cells. Quantitative analysis with total reflection X-ray fluorescence spectrometry showed that after 24 h, 78% of PC grafted, 68-69% of PEG or PC-PEG grafted, and 30% of bare IONPs were taken up by the BBB. Transcytosis of IONPs was time-dependent and after 24 h, 16-17% of PC or PC-PEG mixture grafted IONPs had passed the BBB model, significantly more than PEG grafted or bare IONPs. These findings point out that grafting of IONPs with PC is a viable strategy for improving the uptake and transcytosis of nanoparticles.

A Decade of the Protein Corona.

In this Perspective, we reflect on a decade of research on the protein corona and contemplate its broad implications for future science and engineering at the bio-nano interface. Specifically, we focus on the physical origins and time evolution of the protein corona, differences in the nanoparticle-protein entity in in vitro and in vivo environments, the role of stealth polymers to minimize the formation of the protein corona, relevant computational and theoretical developments, and the "biocorona", a concept extrapolated from the field of nanomedicine. We conclude the Perspective by outlining future directions and opportunities concerning the protein corona in the coming decade.

Cell trafficking of carbon nanotubes based on fluorescence detection.

Cell trafficking of carbon nanotubes (CNTs) is an area of scientific inquiry that has great implications in medicine, biosensing, and environmental science and engineering. The essence of this inquiry resides in the interaction of carbon nanostructures and cell membranes, regulated by the laws of molecular cell biology and the physiochemical properties of the nanostructures. Of equal importance to this inquiry is a description of cellular responses to the integration of man-made materials; yet, how cellular responses may invoke whole-organism level reaction remains unclear. In this chapter, we show three experimental studies, which may be beneficial to obtaining such an understanding. Among the reservoir of methodologies, which have proved of merit, we focus our attention on fluorescence microscopy, one of the most powerful and yet least invasive means of probing nanoparticles in biological systems. Especially, we present the method of fluorescence energy transfer induced between a lysophospholipid molecule and a single-walled CNT upon cellular uptake, and describe coating nanotubes with RNA and suspending fullerenes with phenolic acids for facilitating their translocation across cell membranes and shuttling between cell organelles. Finally, we comment on the perspective of using molecular simulations for facilitating and guiding such experiments.