期刊
BIOMATERIALS
卷 53, 期 -, 页码 137-148出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.02.088
关键词
Platelets; Magnetoliposomes; Atherosclerosis; MRI; SPIO; Liposomes
资金
- Deutsche Forschungsgesellschaft (DFG) [MU2727/3-1, MU2727/6-1]
- International Science Linkages program from the Department of Innovation, Industry, Science and Research (Australia) [CG130101]
- National Heart Foundation of Australia
- Australian Research Council Future Fellowship scheme
- Victorian Government's Operational Infrastructure Support Program
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 7.5 mol% 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 (similar to 86%, similar to 0.22 mol Fe/mol liposomal lipid) and high MRI sensitivity (relaxivity r(2) = 422 s(-1) mM(-1) and r(2)* = 452 s(-1) mM(-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 ex vivo. 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. (C) 2015 Elsevier Ltd. All rights reserved.
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