Zwitterionic polymer-coated ultrasmall superparamagnetic iron oxide nanoparticles with low protein interaction and high biocompatibility

Karina Pombo-García, Stephan Weiss, Kristof Zarschler, Ching-Seng Ang, René Hübner, Johanna Pufe, Sebastian Meister, Jürgen Seidel, Jens Pietzsch, Leone Spiccia, Holger Stephan, Bim Graham

Research output: Contribution to journalArticleResearchpeer-review

Abstract

We report the synthesis and detailed in vitro evaluation of zwitterionic ultrasmall superparamagnetic iron oxide NPs (USPIONs) comprising oleic acid/oleyl alcohol-stabilized magnetite particles (5 nm core diameter) coated with an amphiphilic zwitterionic polymer, poly(maleic anhydride-alt-1-decene) substituted with 3-(dimethylamino)propylamine (PMAL). These particles display a near-neutral zeta potential at pH≥7 and possess high colloidal stability, maintaining a hydrodynamic diameter of ca. 15–20 nm over a wide range of pHs (4–10) and ionic strength (up to 1 m NaCl). They exhibit very low levels of nonspecific protein binding upon exposure to serum, and negligible uptake by phagocytic and non-phagocytic hepatocarcinoma cells, which suggests that they may be able to resist rapid accumulation in the liver and spleen, a common in vivo fate for NPs. The PMAL-USPIONs exhibit very low cytotoxicity and do not elicit an inflammatory response or display hemolytic activity in vitro. Minimal nonspecific uptake by either cancerous or non-cancerous cell lines was observed, an important precondition to achieve highly selective targeting upon further functionalization with an active targeting agent (e.g., antibody or peptide). Overall, this study establishes the considerable potential of PMAL-USPIONs as a platform for the future development of “stealth” NP-based imaging and/or therapeutic agents.
Original languageEnglish
Pages (from-to)959-971
Number of pages13
JournalChemNanoMat
Volume2
Issue number10
DOIs
Publication statusPublished - 2016

Keywords

  • iron oxide nanoparticles
  • macrophages
  • protein corona
  • proteomics
  • zwitterionic coatings

Cite this

Pombo-García, Karina ; Weiss, Stephan ; Zarschler, Kristof ; Ang, Ching-Seng ; Hübner, René ; Pufe, Johanna ; Meister, Sebastian ; Seidel, Jürgen ; Pietzsch, Jens ; Spiccia, Leone ; Stephan, Holger ; Graham, Bim. / Zwitterionic polymer-coated ultrasmall superparamagnetic iron oxide nanoparticles with low protein interaction and high biocompatibility. In: ChemNanoMat. 2016 ; Vol. 2, No. 10. pp. 959-971.
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abstract = "We report the synthesis and detailed in vitro evaluation of zwitterionic ultrasmall superparamagnetic iron oxide NPs (USPIONs) comprising oleic acid/oleyl alcohol-stabilized magnetite particles (5 nm core diameter) coated with an amphiphilic zwitterionic polymer, poly(maleic anhydride-alt-1-decene) substituted with 3-(dimethylamino)propylamine (PMAL). These particles display a near-neutral zeta potential at pH≥7 and possess high colloidal stability, maintaining a hydrodynamic diameter of ca. 15–20 nm over a wide range of pHs (4–10) and ionic strength (up to 1 m NaCl). They exhibit very low levels of nonspecific protein binding upon exposure to serum, and negligible uptake by phagocytic and non-phagocytic hepatocarcinoma cells, which suggests that they may be able to resist rapid accumulation in the liver and spleen, a common in vivo fate for NPs. The PMAL-USPIONs exhibit very low cytotoxicity and do not elicit an inflammatory response or display hemolytic activity in vitro. Minimal nonspecific uptake by either cancerous or non-cancerous cell lines was observed, an important precondition to achieve highly selective targeting upon further functionalization with an active targeting agent (e.g., antibody or peptide). Overall, this study establishes the considerable potential of PMAL-USPIONs as a platform for the future development of “stealth” NP-based imaging and/or therapeutic agents.",
keywords = "iron oxide nanoparticles, macrophages, protein corona, proteomics, zwitterionic coatings",
author = "Karina Pombo-Garc{\'i}a and Stephan Weiss and Kristof Zarschler and Ching-Seng Ang and Ren{\'e} H{\"u}bner and Johanna Pufe and Sebastian Meister and J{\"u}rgen Seidel and Jens Pietzsch and Leone Spiccia and Holger Stephan and Bim Graham",
year = "2016",
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Pombo-García, K, Weiss, S, Zarschler, K, Ang, C-S, Hübner, R, Pufe, J, Meister, S, Seidel, J, Pietzsch, J, Spiccia, L, Stephan, H & Graham, B 2016, 'Zwitterionic polymer-coated ultrasmall superparamagnetic iron oxide nanoparticles with low protein interaction and high biocompatibility' ChemNanoMat, vol. 2, no. 10, pp. 959-971. https://doi.org/10.1002/cnma.201600233

Zwitterionic polymer-coated ultrasmall superparamagnetic iron oxide nanoparticles with low protein interaction and high biocompatibility. / Pombo-García, Karina; Weiss, Stephan; Zarschler, Kristof; Ang, Ching-Seng; Hübner, René; Pufe, Johanna; Meister, Sebastian; Seidel, Jürgen; Pietzsch, Jens; Spiccia, Leone; Stephan, Holger; Graham, Bim.

In: ChemNanoMat, Vol. 2, No. 10, 2016, p. 959-971.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Zwitterionic polymer-coated ultrasmall superparamagnetic iron oxide nanoparticles with low protein interaction and high biocompatibility

AU - Pombo-García, Karina

AU - Weiss, Stephan

AU - Zarschler, Kristof

AU - Ang, Ching-Seng

AU - Hübner, René

AU - Pufe, Johanna

AU - Meister, Sebastian

AU - Seidel, Jürgen

AU - Pietzsch, Jens

AU - Spiccia, Leone

AU - Stephan, Holger

AU - Graham, Bim

PY - 2016

Y1 - 2016

N2 - We report the synthesis and detailed in vitro evaluation of zwitterionic ultrasmall superparamagnetic iron oxide NPs (USPIONs) comprising oleic acid/oleyl alcohol-stabilized magnetite particles (5 nm core diameter) coated with an amphiphilic zwitterionic polymer, poly(maleic anhydride-alt-1-decene) substituted with 3-(dimethylamino)propylamine (PMAL). These particles display a near-neutral zeta potential at pH≥7 and possess high colloidal stability, maintaining a hydrodynamic diameter of ca. 15–20 nm over a wide range of pHs (4–10) and ionic strength (up to 1 m NaCl). They exhibit very low levels of nonspecific protein binding upon exposure to serum, and negligible uptake by phagocytic and non-phagocytic hepatocarcinoma cells, which suggests that they may be able to resist rapid accumulation in the liver and spleen, a common in vivo fate for NPs. The PMAL-USPIONs exhibit very low cytotoxicity and do not elicit an inflammatory response or display hemolytic activity in vitro. Minimal nonspecific uptake by either cancerous or non-cancerous cell lines was observed, an important precondition to achieve highly selective targeting upon further functionalization with an active targeting agent (e.g., antibody or peptide). Overall, this study establishes the considerable potential of PMAL-USPIONs as a platform for the future development of “stealth” NP-based imaging and/or therapeutic agents.

AB - We report the synthesis and detailed in vitro evaluation of zwitterionic ultrasmall superparamagnetic iron oxide NPs (USPIONs) comprising oleic acid/oleyl alcohol-stabilized magnetite particles (5 nm core diameter) coated with an amphiphilic zwitterionic polymer, poly(maleic anhydride-alt-1-decene) substituted with 3-(dimethylamino)propylamine (PMAL). These particles display a near-neutral zeta potential at pH≥7 and possess high colloidal stability, maintaining a hydrodynamic diameter of ca. 15–20 nm over a wide range of pHs (4–10) and ionic strength (up to 1 m NaCl). They exhibit very low levels of nonspecific protein binding upon exposure to serum, and negligible uptake by phagocytic and non-phagocytic hepatocarcinoma cells, which suggests that they may be able to resist rapid accumulation in the liver and spleen, a common in vivo fate for NPs. The PMAL-USPIONs exhibit very low cytotoxicity and do not elicit an inflammatory response or display hemolytic activity in vitro. Minimal nonspecific uptake by either cancerous or non-cancerous cell lines was observed, an important precondition to achieve highly selective targeting upon further functionalization with an active targeting agent (e.g., antibody or peptide). Overall, this study establishes the considerable potential of PMAL-USPIONs as a platform for the future development of “stealth” NP-based imaging and/or therapeutic agents.

KW - iron oxide nanoparticles

KW - macrophages

KW - protein corona

KW - proteomics

KW - zwitterionic coatings

U2 - 10.1002/cnma.201600233

DO - 10.1002/cnma.201600233

M3 - Article

VL - 2

SP - 959

EP - 971

JO - ChemNanoMat

JF - ChemNanoMat

SN - 2199-692X

IS - 10

ER -