Negatively charged hydrophobic nanoparticles inhibit amyloid β-protein fibrillation: The presence of an optimal charge density

Liu, Hongchen; Xie, Baolong; Dong, Xiaoyan; Zhang, Lei; Wang, Yongjian; Liu, Fufeng; Sun, Yan

doi:10.1016/j.reactfunctpolym.2016.04.003

Cited by 36 publications

(28 citation statements)

References 55 publications

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“…Currently, several types of inhibitors that target amyloid aggregation are under development, including small molecule inhibitors, peptides, nanoparticles, antibodies, and proteins . Among them, peptides and peptidomimetics have been extensively studied for their specific interactions with Aβ .…”

Section: Introductionmentioning

confidence: 99%

Design of nonapeptide LVFFARKHH: A bifunctional agent against Cu²⁺‐mediated amyloid β‐protein aggregation and cytotoxicity

Zhang

Dong

et al. 2018

J of Molecular Recognition

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Dysfunctional accumulation of amyloid β-protein (Aβ) mediated by Cu exhibits higher neurotoxicity and accelerates the progress of Alzheimer's disease, so inhibition of Cu -mediated Aβ aggregation and cytotoxicity has been considered as a therapeutic strategy for the disease. Herein, a nonapeptide was designed by linking HH to the C-terminus of a peptide inhibitor of Aβ aggregation, LVFFARK (LK7). We found that the nonapeptide, LK7-HH, possessed dual functionality, including enhanced inhibition capability on Aβ aggregation as compared to LK7, and chelating Cu with a dissociation constant of 5.50 μM. This enabled LK7-HH to arrest the generation of reactive oxygen species catalyzed by Cu or Cu -Aβ complex, and to inhibit Cu -induced Aβ aggregation. Moreover, in contrast with the cytotoxicity of LK7 aggregates, LK7-HH was biocompatible because HH conjugation made its aggregation behavior different from LK7. Thus, LK7-HH efficiently suppressed Cu -mediated Aβ aggregation and cytotoxicity. An equimolar concentration of LK7-HH increased cell viability from 50% to 90% when treating Aβ -Cu complexes. The results provided insights into the roles of HH in enhancing the inhibition of Aβ and Cu -induced Aβ aggregations, in eliminating Cu -induced cytotoxicities by arresting generation of reactive oxygen species, and in making the peptide biocompatible. Therefore, this work would contribute to the design of potent peptide-based inhibitors of Cu -mediated Aβ aggregation and cytotoxicity.

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Section: Introductionmentioning

confidence: 99%

Design of nonapeptide LVFFARKHH: A bifunctional agent against Cu²⁺‐mediated amyloid β‐protein aggregation and cytotoxicity

Zhang

Dong

et al. 2018

J of Molecular Recognition

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“…A dopaminecontaining PEG-based polymer with high density was developed for the retardation of α-synuclein fibrillation [103]. Polymeric NPs can inhibit Aβ fibrillogenesis depending on their surface characteristics [104]. It was found that polymeric NPs inhibit the amyloid extension due to negative surface charges.…”

Section: Surface Chemistrymentioning

confidence: 99%

“…It was found that polymeric NPs inhibit the amyloid extension due to negative surface charges. It was deduced that negative charge distribution van strength the stretching of Aβ42 molecules instead of the formation of amyloid aggregates [104]. Green tea polyphenol epigallocatechin-3-gallate (EGCG) in the form of EGCG NPs (nano-EGCG) are more influential than molecular EGCG in retarding amyloid formation, destabilizing mature protein amyloids, and reducing amyloidogenic cytotoxicity ( Figure 12) [105].…”

Section: Surface Chemistrymentioning

confidence: 99%

A health concern regarding the protein corona, aggregation and disaggregation

Falahati

Attar²,

Sharifi

et al. 2019

Biochimica et Biophysica Acta (BBA) - General Subjects

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A B S T R A C T Nanoparticle (NP)-protein complexes exhibit the "correct identity" of NP in biological media. Therefore, protein-NP interactions should be closely explored to understand and modulate the nature of NPs in medical implementations. This review focuses mainly on the physicochemical parameters such as dimension, surface chemistry, morphology of NPs, and influence of pH on the formation of protein corona and conformational changes of adsorbed proteins by different kinds of techniques. Also, the impact of protein corona on the colloidal stability of NPs is discussed. Uncontrolled protein attachment on NPs may bring unwanted impacts such as protein denaturation and aggregation. In contrast, controlled protein adsorption by optimal concentration, size, pH, and surface modification of NPs may result in potential implementation of NPs as therapeutic agents especially for disaggregation of amyloid fibrils. Also, the effect of NPs-protein corona on reducing the cytotoxicity and clinical implications such as drug delivery, cancer therapy, imaging and diagnosis will be discussed. Validated correlative physicochemical parameters for NP-protein corona formation frequently derived from protein corona fingerprints of NPs which are more valid than the parameters obtained only on the base of NP features. This review may provide useful information regarding the potency as well as the adverse effects of NPs to predict their behavior in vivo.

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“…However, controversial results have been reported on how the polarity of surface charges affects the amyloid aggregation. In the work reported by Liao et al [186], AuNPs (30 nm) with opposite surface charges are prepared by carboxylic and amine functionalization (amine polymeric nanoparticles [187,188], which also emphasize the importance of negative surface charge. However, other studies have shown that the positively charged nanoparticles have a greater inhibition effect.…”

Section: Nanoparticle Based Inhibitorsmentioning

confidence: 99%

“…These contradictory results are attributed to the synergy effect of several factors including the particle's polarity, size, hydrophobicity and particle/peptide ratio. Recent studies have also found that instead of polarity, the surface charge density of particles is the defining factor for the inhibition efficiency [187,191]. and with 10μg/ml C-dots (c).…”

Section: Nanoparticle Based Inhibitorsmentioning

confidence: 99%

Investigation into multifunctional nanoparticles for the detection, imaging and intervention of amyloid

Xia¹

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Amyloid is defined as insoluble, extracellular, proteinous aggregates formed by misfolding of proteins or peptides which are normally soluble. In the human body, amyloid is toxic and can cause cell death. Therefore, the presence of amyloid is linked with several diseases, including Alzheimer's disease (AD), spongiform encephalopathies and type II diabetes, which are also referred as amyloidosis. AD is one of the most well-known amyloidoses. In AD, the amyloid aggregates appear predominantly in the patients' brain, composed by a certain group of peptides known as amyloid beta (Aβ) peptides. Current clinical diagnoses of AD are primarily based on cognitive symptoms. However, it is often too late for intervention when the symptoms are detectable and there is no effective treatment for AD. On the other hand, the onset of amyloid aggregation may start years before the appearance of AD symptoms. Therefore, the detection and intervention of AD related amyloid at the molecular level are expected to be developed as powerful diagnostic and therapeutic methods for AD. Nanoparticle facilitated therapy and diagnosis have recently achieved impressive success in biomedical researches, especially in oncology studies. Compared to small molecule based probes and drugs, nanoparticles are capable to generate more comprehensive diagnosis, enhanced therapeutic effect, and better specific targeting. However, the reported applications of nanoparticles for AD research are still limited. In this context, by identifying the aforementioned research gap, this thesis aims to investigate the potential of nanoparticles for the early detection, imaging, and intervention of amyloid. To fulfill this objective, three nanoparticles: gold nanoparticles (AuNPs), carbon dots (C-dots) and iron oxide nanoparticles (IONPs), have been selected due to their unique physiochemical properties.

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Negatively charged hydrophobic nanoparticles inhibit amyloid β-protein fibrillation: The presence of an optimal charge density

Cited by 36 publications

References 55 publications

Design of nonapeptide LVFFARKHH: A bifunctional agent against Cu²⁺‐mediated amyloid β‐protein aggregation and cytotoxicity

Design of nonapeptide LVFFARKHH: A bifunctional agent against Cu²⁺‐mediated amyloid β‐protein aggregation and cytotoxicity

A health concern regarding the protein corona, aggregation and disaggregation

Investigation into multifunctional nanoparticles for the detection, imaging and intervention of amyloid

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Negatively charged hydrophobic nanoparticles inhibit amyloid β-protein fibrillation: The presence of an optimal charge density

Cited by 36 publications

References 55 publications

Design of nonapeptide LVFFARKHH: A bifunctional agent against Cu2+‐mediated amyloid β‐protein aggregation and cytotoxicity

Design of nonapeptide LVFFARKHH: A bifunctional agent against Cu2+‐mediated amyloid β‐protein aggregation and cytotoxicity

A health concern regarding the protein corona, aggregation and disaggregation

Investigation into multifunctional nanoparticles for the detection, imaging and intervention of amyloid

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Product

Resources

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Design of nonapeptide LVFFARKHH: A bifunctional agent against Cu²⁺‐mediated amyloid β‐protein aggregation and cytotoxicity

Design of nonapeptide LVFFARKHH: A bifunctional agent against Cu²⁺‐mediated amyloid β‐protein aggregation and cytotoxicity