Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging

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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 (<100 nM) 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 1 week. 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. (c) 2012 Elsevier B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2012-10
Language
English
Article Type
Article
Keywords

IRON-OXIDE NANOPARTICLES; MULTIFUNCTIONAL MAGNETIC NANOPARTICLES; BIOMEDICAL APPLICATIONS; CONTRAST AGENTS; THERAPY; DELIVERY; DESIGN; ANGIOGENESIS; TRANSLATION; MARKER

Citation

JOURNAL OF CONTROLLED RELEASE, v.163, no.2, pp.111 - 118

ISSN
0168-3659
DOI
10.1016/j.jconrel.2012.08.029
URI
http://hdl.handle.net/10203/102628
Appears in Collection
BS-Journal Papers(저널논문)
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