Templated polymer replica nanoparticles to facilitate assessment of material-dependent pharmacokinetics and biodistribution

Danzi Song, Jiwei Cui, Huanli Sun, Tri Hung Nguyen, Sheilajen Alcantara, Robert De Rose, Stephen J. Kent, Christopher J H Porter, Frank Caruso

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Surface modification is frequently used to tailor the interactions of nanoparticles with biological systems. In many cases, the chemical nature of the treatments employed to modify the biological interface (for example attachment of hydrophilic polymers or targeting groups) is the focus of attention. However, isolation of the fundamental effects of the materials employed to modify the interface are often confounded by secondary effects imparted by the underlying substrate. Herein, we demonstrate that polymer replica particles templated from degradable mesoporous silica provide a facile means to evaluate the impact of surface modification on the biological interactions of nanomaterials, independent of the substrate. Poly(ethylene glycol) (PEG), poly(N-(2 hydroxypropyl)methacrylamide) (PHPMA), and poly(methacrylic acid) (PMA) were templated onto mesoporous silica and cross-linked and the residual particles were removed. The resulting nanoparticles, comprising interfacial polymer alone, were then investigated using a range of in vitro and in vivo tests. As expected, the PEG particles showed the best stealth properties, and these trends were consistent in both in vitro and in vivo studies. PMA particles showed the highest cell association in cell lines in vitro and were rapidly taken up by monocytes in ex vivo whole blood, properties consistent with the very high in vivo clearance subsequently seen in rats. In contrast, PHPMA particles showed rapid association with both granulocytes and monocytes in ex vivo whole blood, even though in vivo clearance was less rapid than the PMA particles. Rat studies confirmed better systemic exposure for PEG and PHPMA particles when compared to PMA particles. This study provides a new avenue for investigating material-dependent biological behaviors of polymer particles, irrespective of the properties of the underlying core, and provides insights for the selection of polymer particles for future biological applications.
Original languageEnglish
Pages (from-to)33683-33694
Number of pages12
JournalACS Applied Materials and Interfaces
Volume9
Issue number39
DOIs
Publication statusPublished - 1 Jan 2017

Keywords

  • Biodistribution
  • Cell association
  • Mesoporous silica particles
  • Nanoengineering
  • Replica hydrogel particles

Cite this

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title = "Templated polymer replica nanoparticles to facilitate assessment of material-dependent pharmacokinetics and biodistribution",
abstract = "Surface modification is frequently used to tailor the interactions of nanoparticles with biological systems. In many cases, the chemical nature of the treatments employed to modify the biological interface (for example attachment of hydrophilic polymers or targeting groups) is the focus of attention. However, isolation of the fundamental effects of the materials employed to modify the interface are often confounded by secondary effects imparted by the underlying substrate. Herein, we demonstrate that polymer replica particles templated from degradable mesoporous silica provide a facile means to evaluate the impact of surface modification on the biological interactions of nanomaterials, independent of the substrate. Poly(ethylene glycol) (PEG), poly(N-(2 hydroxypropyl)methacrylamide) (PHPMA), and poly(methacrylic acid) (PMA) were templated onto mesoporous silica and cross-linked and the residual particles were removed. The resulting nanoparticles, comprising interfacial polymer alone, were then investigated using a range of in vitro and in vivo tests. As expected, the PEG particles showed the best stealth properties, and these trends were consistent in both in vitro and in vivo studies. PMA particles showed the highest cell association in cell lines in vitro and were rapidly taken up by monocytes in ex vivo whole blood, properties consistent with the very high in vivo clearance subsequently seen in rats. In contrast, PHPMA particles showed rapid association with both granulocytes and monocytes in ex vivo whole blood, even though in vivo clearance was less rapid than the PMA particles. Rat studies confirmed better systemic exposure for PEG and PHPMA particles when compared to PMA particles. This study provides a new avenue for investigating material-dependent biological behaviors of polymer particles, irrespective of the properties of the underlying core, and provides insights for the selection of polymer particles for future biological applications.",
keywords = "Biodistribution, Cell association, Mesoporous silica particles, Nanoengineering, Replica hydrogel particles",
author = "Danzi Song and Jiwei Cui and Huanli Sun and Nguyen, {Tri Hung} and Sheilajen Alcantara and {De Rose}, Robert and Kent, {Stephen J.} and Porter, {Christopher J H} and Frank Caruso",
year = "2017",
month = "1",
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doi = "10.1021/acsami.7b11579",
language = "English",
volume = "9",
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journal = "ACS Applied Materials and Interfaces",
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Templated polymer replica nanoparticles to facilitate assessment of material-dependent pharmacokinetics and biodistribution. / Song, Danzi; Cui, Jiwei; Sun, Huanli; Nguyen, Tri Hung; Alcantara, Sheilajen; De Rose, Robert; Kent, Stephen J.; Porter, Christopher J H; Caruso, Frank.

In: ACS Applied Materials and Interfaces, Vol. 9, No. 39, 01.01.2017, p. 33683-33694.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Templated polymer replica nanoparticles to facilitate assessment of material-dependent pharmacokinetics and biodistribution

AU - Song, Danzi

AU - Cui, Jiwei

AU - Sun, Huanli

AU - Nguyen, Tri Hung

AU - Alcantara, Sheilajen

AU - De Rose, Robert

AU - Kent, Stephen J.

AU - Porter, Christopher J H

AU - Caruso, Frank

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Surface modification is frequently used to tailor the interactions of nanoparticles with biological systems. In many cases, the chemical nature of the treatments employed to modify the biological interface (for example attachment of hydrophilic polymers or targeting groups) is the focus of attention. However, isolation of the fundamental effects of the materials employed to modify the interface are often confounded by secondary effects imparted by the underlying substrate. Herein, we demonstrate that polymer replica particles templated from degradable mesoporous silica provide a facile means to evaluate the impact of surface modification on the biological interactions of nanomaterials, independent of the substrate. Poly(ethylene glycol) (PEG), poly(N-(2 hydroxypropyl)methacrylamide) (PHPMA), and poly(methacrylic acid) (PMA) were templated onto mesoporous silica and cross-linked and the residual particles were removed. The resulting nanoparticles, comprising interfacial polymer alone, were then investigated using a range of in vitro and in vivo tests. As expected, the PEG particles showed the best stealth properties, and these trends were consistent in both in vitro and in vivo studies. PMA particles showed the highest cell association in cell lines in vitro and were rapidly taken up by monocytes in ex vivo whole blood, properties consistent with the very high in vivo clearance subsequently seen in rats. In contrast, PHPMA particles showed rapid association with both granulocytes and monocytes in ex vivo whole blood, even though in vivo clearance was less rapid than the PMA particles. Rat studies confirmed better systemic exposure for PEG and PHPMA particles when compared to PMA particles. This study provides a new avenue for investigating material-dependent biological behaviors of polymer particles, irrespective of the properties of the underlying core, and provides insights for the selection of polymer particles for future biological applications.

AB - Surface modification is frequently used to tailor the interactions of nanoparticles with biological systems. In many cases, the chemical nature of the treatments employed to modify the biological interface (for example attachment of hydrophilic polymers or targeting groups) is the focus of attention. However, isolation of the fundamental effects of the materials employed to modify the interface are often confounded by secondary effects imparted by the underlying substrate. Herein, we demonstrate that polymer replica particles templated from degradable mesoporous silica provide a facile means to evaluate the impact of surface modification on the biological interactions of nanomaterials, independent of the substrate. Poly(ethylene glycol) (PEG), poly(N-(2 hydroxypropyl)methacrylamide) (PHPMA), and poly(methacrylic acid) (PMA) were templated onto mesoporous silica and cross-linked and the residual particles were removed. The resulting nanoparticles, comprising interfacial polymer alone, were then investigated using a range of in vitro and in vivo tests. As expected, the PEG particles showed the best stealth properties, and these trends were consistent in both in vitro and in vivo studies. PMA particles showed the highest cell association in cell lines in vitro and were rapidly taken up by monocytes in ex vivo whole blood, properties consistent with the very high in vivo clearance subsequently seen in rats. In contrast, PHPMA particles showed rapid association with both granulocytes and monocytes in ex vivo whole blood, even though in vivo clearance was less rapid than the PMA particles. Rat studies confirmed better systemic exposure for PEG and PHPMA particles when compared to PMA particles. This study provides a new avenue for investigating material-dependent biological behaviors of polymer particles, irrespective of the properties of the underlying core, and provides insights for the selection of polymer particles for future biological applications.

KW - Biodistribution

KW - Cell association

KW - Mesoporous silica particles

KW - Nanoengineering

KW - Replica hydrogel particles

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DO - 10.1021/acsami.7b11579

M3 - Article

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EP - 33694

JO - ACS Applied Materials and Interfaces

JF - ACS Applied Materials and Interfaces

SN - 1944-8244

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