title: Recognition of dextran-superparamagnetic iron oxide nanoparticle conjugates (Feridex) via macrophage scavenger receptor charged domains.
abstract: 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.
authors.affiliation: Moores Cancer Center, School of Medicine, ‡Department of Neurosciences, and ⊥San Diego Supercomputer Center, University of California San Diego , La Jolla, California, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chao
authors.forename: Milan
authors.initials: M
authors.lastname: Makale
authors.forename: Priya Prakash
authors.initials: PP
authors.lastname: Karmali
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Sharikov
authors.forename: Igor
authors.initials: I
authors.lastname: Tsigelny
authors.forename: Sergei
authors.initials: S
authors.lastname: Merkulov
authors.forename: Santosh
authors.initials: S
authors.lastname: Kesari
authors.forename: Wolf
authors.initials: W
authors.lastname: Wrasidlo
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
authors.forename: Dmitri
authors.initials: D
authors.lastname: Simberg
mesh_terms: D003001:Cloning, Molecular; D024042:Collagen Type I / Q000378:metabolism; D003287:Contrast Media / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008958:Models, Molecular; D053758:Nanoparticles / Q000378:metabolism* / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D051116:Receptors, Scavenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D051116:Receptors, Scavenger; C065507:ferumoxides