Design and characterization of antithrombotic ClEKnsTy-Au nanoparticles as diagnostic and therapeutic reagents

Xie, Changsheng; Zhang, Lin

doi:10.1039/d3cp01000g

Cited by 2 publications

(2 citation statements)

References 49 publications

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“…Understanding how ligand properties influence interactions between NPs and cell membranes is of particular biomedical importance. ,− For example, NP adsorption to the cell membrane can drive intracellular transport, which is critical for applications requiring delivery of NPs to the cell interior, but may also cause membrane disruption and cytotoxicity. , Given the complex composition of the cell membrane, simplified lipid bilayer systems, such as supported lipid bilayers (SLBs) and lipid vesicles with a small number of components, are routinely used experimentally as model membranes to enable mechanistic studies of NP–bilayer interactions . Experimental studies of NP–bilayer interactions can be related to biologically relevant behaviors; for example, the adsorption of NPs to lipid bilayers correlates with endocytic uptake, NP-induced disruption of lipid bilayers correlates with cytotoxicity, and the insertion of amphiphilic NPs into lipid bilayers correlates with nonendocytic cell entry .…”

Section: Introductionmentioning

confidence: 99%

Ligand Lipophilicity Determines Molecular Mechanisms of Nanoparticle Adsorption to Lipid Bilayers

Huang-Zhu,

Sheavly,

Chew

et al. 2024

ACS Nano

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The interactions of ligand-functionalized nanoparticles with the cell membrane affect cellular uptake, cytotoxicity, and related behaviors, but relating these interactions to ligand properties remains challenging. In this work, we perform coarse-grained molecular dynamics simulations to study how the adsorption of ligandfunctionalized cationic gold nanoparticles (NPs) to a singlecomponent lipid bilayer (as a model cell membrane) is influenced by ligand end group lipophilicity. A set of 2 nm diameter NPs, each coated with a monolayer of organic ligands that differ only in their end groups, was simulated to mimic NPs recently studied experimentally. Metadynamics calculations were performed to determine key features of the free energy landscape for adsorption as a function of the distance of the NP from the bilayer and the number of NP−lipid contacts. These simulations revealed that NP adsorption is thermodynamically favorable for all NPs due to the extraction of lipids from the bilayer and into the NP monolayer. To resolve ligand-dependent differences in adsorption behavior, string method calculations were performed to compute minimum free energy pathways for adsorption. These calculations revealed a surprising nonmonotonic dependence of the free energy barrier for adsorption on ligand end group lipophilicity. Large free energy barriers are predicted for the least lipophilic end groups because favorable NP−lipid contacts are initiated only through the unfavorable protrusion of lipid tail groups out of the bilayer. The smallest free energy barriers are predicted for end groups of intermediate lipophilicity which promote NP−lipid contacts by intercalating within the bilayer. Unexpectedly, large free energy barriers are also predicted for the most lipophilic end groups which remain sequestered within the ligand monolayer rather than intercalating within the bilayer. These trends are broadly in agreement with past experimental measurements and reveal how subtle variations in ligand lipophilicity dictate adsorption mechanisms and associated kinetics by influencing the interplay of lipid−ligand interactions.

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Section: Introductionmentioning

confidence: 99%

Ligand Lipophilicity Determines Molecular Mechanisms of Nanoparticle Adsorption to Lipid Bilayers

Huang-Zhu,

Sheavly,

Chew

et al. 2024

ACS Nano

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“…[9][10][11][12][13][14][15][16] On the other hand, functional gold nanomaterials have been widely demonstrated to hold great therapeutic prospects in the treatment of thrombosis, presumably using gold nanoparticles as driven antithrombotic carriers. 5 Gold nanoparticles have been found to treat thrombosis by affecting fibrin formation, 17 preventing platelet activation, 18 and photothermal thrombolysis. 19 In addition, gold nanoparticles can also target activated neutrophil attachment to treat immunothrombosis associated with neutrophil adhesion in antiphospholipid syndrome.…”

mentioning

confidence: 99%

Mercaptopyrimidine-templated gold nanoclusters for antithrombotic therapy

Dai,

Lei,

Zhang

et al. 2024

J. Mater. Chem. B

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Design and characterization of antithrombotic ClEKnsTy-Au nanoparticles as diagnostic and therapeutic reagents

Abstract: Thrombosis can cause various cardiovascular diseases, which seriously endangers human life. Development of diagnostic and therapeutic reagents for thrombosis at an early stage would be helpful for the improvement of...

Cited by 2 publications

References 49 publications

Ligand Lipophilicity Determines Molecular Mechanisms of Nanoparticle Adsorption to Lipid Bilayers

Ligand Lipophilicity Determines Molecular Mechanisms of Nanoparticle Adsorption to Lipid Bilayers

Mercaptopyrimidine-templated gold nanoclusters for antithrombotic therapy

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