Thiol-Reactive Star Polymers Display Enhanced Association with Distinct Human Blood Components

Joshua J. Glass, Yang Li, Robert De Rose, Angus Johnston, Ewa I. Czuba, Song Yang Khor, John F Quinn, Michael R. Whittaker, Thomas P Davis, Stephen J Kent

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Directing nanoparticles to specific cell types using nonantibody-based methods is of increasing interest. Thiol-reactive nanoparticles can enhance the efficiency of cargo delivery into specific cells through interactions with cell-surface proteins. However, studies to date using this technique have been largely limited to immortalized cell lines or rodents, and the utility of this technology on primary human cells is unknown. Herein, we used RAFT polymerization to prepare pyridyl disulfide (PDS)-functionalized star polymers with a methoxy-poly(ethylene glycol) brush corona and a fluorescently labeled cross-linked core using an arm-first method. PDS star polymers were examined for their interaction with primary human blood components: six separate white blood cell subsets, as well as red blood cells and platelets. Compared with control star polymers, thiol-reactive nanoparticles displayed enhanced association with white blood cells at 37 °C, particularly the phagocytic monocyte, granulocyte, and dendritic cell subsets. Platelets associated with more PDS than control nanoparticles at both 37 °C and on ice, but they were not activated in the duration examined. Association with red blood cells was minor but still enhanced with PDS nanoparticles. Thiol-reactive nanoparticles represent a useful strategy to target primary human immune cell subsets for improved nanoparticle delivery. © 2017 American Chemical Society.
Original languageEnglish
Pages (from-to)12182-12194
Number of pages13
JournalACS Applied Materials and Interfaces
Volume9
Issue number14
DOIs
Publication statusPublished - 12 Apr 2017

Keywords

  • star polymers
  • blood
  • thiols
  • platelets
  • targeting

Cite this

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title = "Thiol-Reactive Star Polymers Display Enhanced Association with Distinct Human Blood Components",
abstract = "Directing nanoparticles to specific cell types using nonantibody-based methods is of increasing interest. Thiol-reactive nanoparticles can enhance the efficiency of cargo delivery into specific cells through interactions with cell-surface proteins. However, studies to date using this technique have been largely limited to immortalized cell lines or rodents, and the utility of this technology on primary human cells is unknown. Herein, we used RAFT polymerization to prepare pyridyl disulfide (PDS)-functionalized star polymers with a methoxy-poly(ethylene glycol) brush corona and a fluorescently labeled cross-linked core using an arm-first method. PDS star polymers were examined for their interaction with primary human blood components: six separate white blood cell subsets, as well as red blood cells and platelets. Compared with control star polymers, thiol-reactive nanoparticles displayed enhanced association with white blood cells at 37 °C, particularly the phagocytic monocyte, granulocyte, and dendritic cell subsets. Platelets associated with more PDS than control nanoparticles at both 37 °C and on ice, but they were not activated in the duration examined. Association with red blood cells was minor but still enhanced with PDS nanoparticles. Thiol-reactive nanoparticles represent a useful strategy to target primary human immune cell subsets for improved nanoparticle delivery. {\circledC} 2017 American Chemical Society.",
keywords = "star polymers, blood, thiols, platelets, targeting",
author = "Glass, {Joshua J.} and Yang Li and {De Rose}, Robert and Angus Johnston and Czuba, {Ewa I.} and Khor, {Song Yang} and Quinn, {John F} and Whittaker, {Michael R.} and Davis, {Thomas P} and Kent, {Stephen J}",
year = "2017",
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day = "12",
doi = "DOI: 10.1021/acsami.6b15942",
language = "English",
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Thiol-Reactive Star Polymers Display Enhanced Association with Distinct Human Blood Components. / Glass, Joshua J.; Li, Yang; De Rose, Robert; Johnston, Angus; Czuba, Ewa I.; Khor, Song Yang; Quinn, John F; Whittaker, Michael R.; Davis, Thomas P; Kent, Stephen J.

In: ACS Applied Materials and Interfaces, Vol. 9, No. 14, 12.04.2017, p. 12182-12194.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Thiol-Reactive Star Polymers Display Enhanced Association with Distinct Human Blood Components

AU - Glass, Joshua J.

AU - Li, Yang

AU - De Rose, Robert

AU - Johnston, Angus

AU - Czuba, Ewa I.

AU - Khor, Song Yang

AU - Quinn, John F

AU - Whittaker, Michael R.

AU - Davis, Thomas P

AU - Kent, Stephen J

PY - 2017/4/12

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AB - Directing nanoparticles to specific cell types using nonantibody-based methods is of increasing interest. Thiol-reactive nanoparticles can enhance the efficiency of cargo delivery into specific cells through interactions with cell-surface proteins. However, studies to date using this technique have been largely limited to immortalized cell lines or rodents, and the utility of this technology on primary human cells is unknown. Herein, we used RAFT polymerization to prepare pyridyl disulfide (PDS)-functionalized star polymers with a methoxy-poly(ethylene glycol) brush corona and a fluorescently labeled cross-linked core using an arm-first method. PDS star polymers were examined for their interaction with primary human blood components: six separate white blood cell subsets, as well as red blood cells and platelets. Compared with control star polymers, thiol-reactive nanoparticles displayed enhanced association with white blood cells at 37 °C, particularly the phagocytic monocyte, granulocyte, and dendritic cell subsets. Platelets associated with more PDS than control nanoparticles at both 37 °C and on ice, but they were not activated in the duration examined. Association with red blood cells was minor but still enhanced with PDS nanoparticles. Thiol-reactive nanoparticles represent a useful strategy to target primary human immune cell subsets for improved nanoparticle delivery. © 2017 American Chemical Society.

KW - star polymers

KW - blood

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KW - targeting

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