Recognition of Dextran–Superparamagnetic Iron Oxide Nanoparticle Conjugates (Feridex) via Macrophage Scavenger Receptor Charged Domains

Dextran-coated superparamagnetic iron oxide nanoparticles (dextran–SPIO conjugates) offer the attractive possibility of enhancing MRI imaging sensitivity so that small or diffuse lesions can be detected. However, systemically injected SPIOs are rapidly removed by macrophages. We engineered embryonic...

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Published inBioconjugate chemistry Vol. 23; no. 5; pp. 1003 - 1009
Main Authors Chao, Ying, Makale, Milan, Karmali, Priya Prakash, Sharikov, Yuriy, Tsigelny, Igor, Merkulov, Sergei, Kesari, Santosh, Wrasidlo, Wolf, Ruoslahti, Erkki, Simberg, Dmitri
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 16.05.2012
Subjects
Amino acids
Biochemistry
Cells
Cloning, Molecular
Collagen
Collagen Type I - metabolism
Contrast Media - metabolism
Dextrans - metabolism
HEK293 Cells
Humans
Macrophages - metabolism
Magnetic Resonance Imaging
Magnetite Nanoparticles
Models, Molecular
Nanoparticles
Nanoparticles - metabolism
Nanoparticles - ultrastructure
NMR
Nuclear magnetic resonance
Protein Structure, Tertiary
Receptors, Scavenger - chemistry
Receptors, Scavenger - genetics
Receptors, Scavenger - metabolism
T cell receptors
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Summary:Dextran-coated superparamagnetic iron oxide nanoparticles (dextran–SPIO conjugates) offer the attractive possibility of enhancing MRI imaging sensitivity so that small or diffuse lesions can be detected. However, systemically injected SPIOs are rapidly removed by macrophages. We engineered embryonic cells (HEK293T) to express major macrophage scavenger receptor (SR) subtypes including SR-AI, MARCO, and endothelial receptor collectin-12. These SRs possess a positively charged collagen-like (CL) domain and they promoted SPIO uptake, while the charge neutral lipoprotein receptor SR-BI did not. In silico modeling indicated a positive net charge on the CL domain and a net negative charge on the cysteine-rich (CR) domain of MARCO and SR-AI. In vitro experiments revealed that CR domain deletion in SR-AI boosted uptake of SPIO 3-fold, while deletion of MARCO’s CR domain abolished this uptake. These data suggest that future studies might productively focus on the validation and further exploration of SR charge fields in SPIO recognition.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc200685a