title: Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging.
abstract: Fibronectin extra domain B (EDB) is specifically expressed in cancer-associated blood vessels and extracellular matrix, and thus is a promising cancer biomarker. Very recently, we developed a novel class of high-affinity (<100nM) peptides, termed 'aptides', that specifically bind a variety of protein targets. Here, we describe superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with EDB-specific aptides for use in targeted magnetic resonance imaging (MRI) of cancer. An anti-EDB aptide (APT(EDB)) containing an additional cysteine residue reacted with maleimide-terminated, PEGylated phospholipid (Mal-PEG(2000)-DSPE) to give an aptide-conjugated PEGylated phospholipid (APT(EDB)-PEG(2000)-DSPE). A nanoemulsion method was then used to coat oleic acid-stabilized SPIONs with amphiphilic phospholipids, including APT(EDB)-PEG(2000)-DSPE, methoxy-PEG(2000)-DSPE, and rhodamine-DMPE. The resulting nanoparticles (APT(EDB)-SPIONs) had a hydrodynamic size of less than 50 nm and remained stable in an aqueous solution for at least 1week. In in vitro studies, APT(EDB)-SPIONs showed specific uptake by EDB-overexpressing cell lines. In an in vivo Lewis lung carcinoma model that expresses a high level of the target EDB protein, MRI clearly revealed that APT(EDB)-SPIONs injected via the tail vein specifically accumulated at the tumor site. Non-targeting SPIONs lacking the anti-EDB aptide showed much lower uptake in tumor tissues than did aptide-conjugated nanoparticles. Further, we confirmed that the distribution of nanoparticles within the tumor tissue was well correlated with the areas where EDB was expressed. Our APT(EDB)-SPIONs hold high potential as a specific imaging modality for the detection of EDB-overexpressing tumors.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, 123 Cheomdangwagi-ro, Buk-gu, Gwangju 500-712, Republic of Korea.
authors.forename: Jinho
authors.initials: J
authors.lastname: Park
authors.forename: Sunghyun
authors.initials: S
authors.lastname: Kim
authors.forename: Phei Er
authors.initials: PE
authors.lastname: Saw
authors.forename: In-Hyun
authors.initials: IH
authors.lastname: Lee
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Yu
authors.forename: Minsik
authors.initials: M
authors.lastname: Kim
authors.forename: Kwangyeol
authors.initials: K
authors.lastname: Lee
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Yong Yeon
authors.initials: YY
authors.lastname: Jeong
authors.forename: Sangyong
authors.initials: S
authors.lastname: Jon
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000175:diagnosis / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D005353:Fibronectins / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000737:chemistry
chemical_list: D005290:Ferric Compounds; D005353:Fibronectins; D010455:Peptides; C000499:ferric oxide