Immuno-magnetoliposomes targeting activated platelets as a potentially human-compatible MRI contrast agent for targeting atherothrombosis

S. Meier, G. Pütz, U. Massing, C. E. Hagemeyer, D. von Elverfeldt, M. Meissner, K. Ardipradja, S. Barnert, K. Peter, C. Bode, R. Schubert, C. Von Zur Muhlen

Research output: Contribution to journalArticleResearchpeer-review

Abstract

To detect unstable atherosclerotic plaques early and noninvasively would be of great clinical interest. Activated platelets are an interesting molecular target for detecting early lesions or unstable plaques. We therefore developed an MRI contrast agent consisting of magnetoliposomes (ML) linked to an antibody (anti-LIBS) specifically targeting the ligand-induced binding site of the activated GPIIb/IIIa receptor of platelets. ML were prepared by dual centrifugation (DC). ML pegylation up to a total PEG content of 7.5mol positively influenced the stability and amount of entrapped SPIOs, and also reduced SPIO-membrane interactions, while higher PEG contents destabilized PEG-ML. Stable anti-LIBS-ML with high amounts of entrapped SPIOs ( 86 , 0.22mol Fe/mol liposomal lipid) and high MRI sensitivity (relaxivity r2=422s-1mM-1 and r2*=452s-1mM-1) were obtained by coupling anti-LIBS to ML in a two-step post-insertion technique. We confirmed specific binding to the GPIIb/IIIa receptor s activated conformation on activated human platelets and cell lines expressing activated GPIIb/IIIa receptor exvivo. The immuno-ML obtained in this study constitute an important step towards developing a potentially human-compatible MRI contrast agent for the timely detection of plaque rupture by targeting activated platelets.
Original languageEnglish
Pages (from-to)137 - 148
Number of pages12
JournalBiomaterials
Volume53
Issue number1
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • platelets
  • magnetoliposomes
  • atherosclerosis
  • MRI
  • SPIO
  • liposomes

Cite this

Meier, S. ; Pütz, G. ; Massing, U. ; Hagemeyer, C. E. ; von Elverfeldt, D. ; Meissner, M. ; Ardipradja, K. ; Barnert, S. ; Peter, K. ; Bode, C. ; Schubert, R. ; Von Zur Muhlen, C. / Immuno-magnetoliposomes targeting activated platelets as a potentially human-compatible MRI contrast agent for targeting atherothrombosis. In: Biomaterials. 2015 ; Vol. 53, No. 1. pp. 137 - 148.
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abstract = "To detect unstable atherosclerotic plaques early and noninvasively would be of great clinical interest. Activated platelets are an interesting molecular target for detecting early lesions or unstable plaques. We therefore developed an MRI contrast agent consisting of magnetoliposomes (ML) linked to an antibody (anti-LIBS) specifically targeting the ligand-induced binding site of the activated GPIIb/IIIa receptor of platelets. ML were prepared by dual centrifugation (DC). ML pegylation up to a total PEG content of 7.5mol positively influenced the stability and amount of entrapped SPIOs, and also reduced SPIO-membrane interactions, while higher PEG contents destabilized PEG-ML. Stable anti-LIBS-ML with high amounts of entrapped SPIOs ( 86 , 0.22mol Fe/mol liposomal lipid) and high MRI sensitivity (relaxivity r2=422s-1mM-1 and r2*=452s-1mM-1) were obtained by coupling anti-LIBS to ML in a two-step post-insertion technique. We confirmed specific binding to the GPIIb/IIIa receptor s activated conformation on activated human platelets and cell lines expressing activated GPIIb/IIIa receptor exvivo. The immuno-ML obtained in this study constitute an important step towards developing a potentially human-compatible MRI contrast agent for the timely detection of plaque rupture by targeting activated platelets.",
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author = "S. Meier and G. P{\"u}tz and U. Massing and Hagemeyer, {C. E.} and {von Elverfeldt}, D. and M. Meissner and K. Ardipradja and S. Barnert and K. Peter and C. Bode and R. Schubert and {Von Zur Muhlen}, C.",
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Meier, S, Pütz, G, Massing, U, Hagemeyer, CE, von Elverfeldt, D, Meissner, M, Ardipradja, K, Barnert, S, Peter, K, Bode, C, Schubert, R & Von Zur Muhlen, C 2015, 'Immuno-magnetoliposomes targeting activated platelets as a potentially human-compatible MRI contrast agent for targeting atherothrombosis', Biomaterials, vol. 53, no. 1, pp. 137 - 148. https://doi.org/10.1016/j.biomaterials.2015.02.088

Immuno-magnetoliposomes targeting activated platelets as a potentially human-compatible MRI contrast agent for targeting atherothrombosis. / Meier, S.; Pütz, G.; Massing, U.; Hagemeyer, C. E.; von Elverfeldt, D.; Meissner, M.; Ardipradja, K.; Barnert, S.; Peter, K.; Bode, C.; Schubert, R.; Von Zur Muhlen, C.

In: Biomaterials, Vol. 53, No. 1, 2015, p. 137 - 148.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Immuno-magnetoliposomes targeting activated platelets as a potentially human-compatible MRI contrast agent for targeting atherothrombosis

AU - Meier, S.

AU - Pütz, G.

AU - Massing, U.

AU - Hagemeyer, C. E.

AU - von Elverfeldt, D.

AU - Meissner, M.

AU - Ardipradja, K.

AU - Barnert, S.

AU - Peter, K.

AU - Bode, C.

AU - Schubert, R.

AU - Von Zur Muhlen, C.

PY - 2015

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N2 - To detect unstable atherosclerotic plaques early and noninvasively would be of great clinical interest. Activated platelets are an interesting molecular target for detecting early lesions or unstable plaques. We therefore developed an MRI contrast agent consisting of magnetoliposomes (ML) linked to an antibody (anti-LIBS) specifically targeting the ligand-induced binding site of the activated GPIIb/IIIa receptor of platelets. ML were prepared by dual centrifugation (DC). ML pegylation up to a total PEG content of 7.5mol positively influenced the stability and amount of entrapped SPIOs, and also reduced SPIO-membrane interactions, while higher PEG contents destabilized PEG-ML. Stable anti-LIBS-ML with high amounts of entrapped SPIOs ( 86 , 0.22mol Fe/mol liposomal lipid) and high MRI sensitivity (relaxivity r2=422s-1mM-1 and r2*=452s-1mM-1) were obtained by coupling anti-LIBS to ML in a two-step post-insertion technique. We confirmed specific binding to the GPIIb/IIIa receptor s activated conformation on activated human platelets and cell lines expressing activated GPIIb/IIIa receptor exvivo. The immuno-ML obtained in this study constitute an important step towards developing a potentially human-compatible MRI contrast agent for the timely detection of plaque rupture by targeting activated platelets.

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KW - platelets

KW - magnetoliposomes

KW - atherosclerosis

KW - MRI

KW - SPIO

KW - liposomes

UR - http://www.sciencedirect.com/science/article/pii/S0142961215002185

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DO - 10.1016/j.biomaterials.2015.02.088

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