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Nano Research 2020, 13(10): 2697-2705 https://doi.org/10.1007/s12274-020-2912-8
Research Article | Open Access | Issue | Published: 05 October 2020

Controlling human platelet activation with calcium-binding nanoparticles

Show Author's Information David Cabrera1,  Karen Walker2,  Sandhya Moise1,3,  Neil D. Telling1,  Alan G. S. Harper1,4( )
School of Pharmacy and Bioengineering, Keele University, Guy Hilton Research Centre, Thornburrow Drive, Hartshill, Stoke-on-Trent ST4 7QB, UK
Central Electron Microscope Unit, School of Life Sciences, Keele University, Newcastle-under-Lyme, Staffordshire, ST5 5BG, UK
Department of Chemical Engineering, University of Bath, Bath BA2 7AY, UK
School of Medicine, Keele University, Newcastle-under-Lyme, Staffordshire, ST5 5BG, UK
Keywords:
nanoparticles, nanochelators, human platelets, open canalicular system, calcium signaling
Topics:
Blood vessels Cell membranes Iron oxidesPatient treatment
Cite this article:
Cabrera D, Walker K, Moise S, et al. Controlling human platelet activation with calcium-binding nanoparticles. Nano Research, 2020, 13(10): 2697-2705. https://doi.org/10.1007/s12274-020-2912-8
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Abstract Full text Electronic supplementary material About this article

Human platelets aggregate at sites of blood vessel damage in response to a rise in their cytosolic calcium concentration. Controlling these cytosolic calcium rises would provide a method to inhibit platelet activation and prevent the unwanted blood clots that causes heart attack and strokes. Previously we have predicted that calcium accumulation within the lumen of an infolded portion of the platelet plasma membrane called the open canalicular system (OCS) is essential for maintaining this cytosolic calcium rise. Due to its nanometer dimensions of the OCS, it has been difficult to measure or interfere with the predicted luminal calcium accumulation. Here we utilise iron oxide magnetic nanoparticles coated with the known calcium chelator, citrate, to create calcium-binding nanoparticles. These were used to assess whether an OCS calcium store plays a role in controlling the dynamics of human platelet activation and aggregation. We demonstrate that citrate-coated nanoparticles are rapidly and selectively uptaken into the OCS of activated human platelets, where they act to buffer the accumulation of calcium there. Treatment with these calcium-binding nanoparticles reduced thrombin-evoked cytosolic calcium rises, and slowed platelet aggregation and clot retraction in human platelets. In contrast, nanoparticles that cannot bind calcium have no effect. This study demonstrates that the OCS acts as a key source of calcium for maintaining cytosolic calcium rises and accelerating platelet aggregation, and that calcium-binding nanoparticles targeted to the OCS could provide an anti-platelet therapy to treat patients at risk of suffering heart attacks or strokes.


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About this article

Controlling human platelet activation with calcium-binding nanoparticles

Show Author's information David Cabrera1, Karen Walker2, Sandhya Moise1,3, Neil D. Telling1, Alan G. S. Harper1,4( )
School of Pharmacy and Bioengineering, Keele University, Guy Hilton Research Centre, Thornburrow Drive, Hartshill, Stoke-on-Trent ST4 7QB, UK
Central Electron Microscope Unit, School of Life Sciences, Keele University, Newcastle-under-Lyme, Staffordshire, ST5 5BG, UK
Department of Chemical Engineering, University of Bath, Bath BA2 7AY, UK
School of Medicine, Keele University, Newcastle-under-Lyme, Staffordshire, ST5 5BG, UK

Abstract

Human platelets aggregate at sites of blood vessel damage in response to a rise in their cytosolic calcium concentration. Controlling these cytosolic calcium rises would provide a method to inhibit platelet activation and prevent the unwanted blood clots that causes heart attack and strokes. Previously we have predicted that calcium accumulation within the lumen of an infolded portion of the platelet plasma membrane called the open canalicular system (OCS) is essential for maintaining this cytosolic calcium rise. Due to its nanometer dimensions of the OCS, it has been difficult to measure or interfere with the predicted luminal calcium accumulation. Here we utilise iron oxide magnetic nanoparticles coated with the known calcium chelator, citrate, to create calcium-binding nanoparticles. These were used to assess whether an OCS calcium store plays a role in controlling the dynamics of human platelet activation and aggregation. We demonstrate that citrate-coated nanoparticles are rapidly and selectively uptaken into the OCS of activated human platelets, where they act to buffer the accumulation of calcium there. Treatment with these calcium-binding nanoparticles reduced thrombin-evoked cytosolic calcium rises, and slowed platelet aggregation and clot retraction in human platelets. In contrast, nanoparticles that cannot bind calcium have no effect. This study demonstrates that the OCS acts as a key source of calcium for maintaining cytosolic calcium rises and accelerating platelet aggregation, and that calcium-binding nanoparticles targeted to the OCS could provide an anti-platelet therapy to treat patients at risk of suffering heart attacks or strokes.

Keywords: nanoparticles, nanochelators, human platelets, open canalicular system, calcium signaling

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Publication history

Received: 03 April 2020
Revised: 29 May 2020
Accepted: 03 June 2020
Published: 05 October 2020
Issue date: October 2020

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© The Author(s) 2020

Acknowledgements

Authors are deeply acknowledged to the Wellcome Trust for funding support (Seed Award in Science, Project grant no 207617/Z/17/Z).

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