title: Active targeting using HER-2-affibody-conjugated nanoparticles enabled sensitive and specific imaging of orthotopic HER-2 positive ovarian tumors.
abstract: Despite advances in cancer diagnosis and treatment, ovarian cancer remains one of the most fatal cancer types. The development of targeted nanoparticle imaging probes and therapeutics offers promising approaches for early detection and effective treatment of ovarian cancer. In this study, HER-2 targeted magnetic iron oxide nanoparticles (IONPs) are developed by conjugating a high affinity and small size HER-2 affibody that is labeled with a unique near infrared dye (NIR-830) to the nanoparticles. Using a clinically relevant orthotopic human ovarian tumor xenograft model, it is shown that HER-2 targeted IONPs are selectively delivered into both primary and disseminated ovarian tumors, enabling non-invasive optical and MR imaging of the tumors as small as 1 mm in the peritoneal cavity. It is determined that HER-2 targeted delivery of the IONPs is essential for specific and sensitive imaging of the HER-2 positive tumor since we are unable to detect the imaging signal in the tumors following systemic delivery of non-targeted IONPs into the mice bearing HER-2 positive SKOV3 tumors. Furthermore, imaging signals and the IONPs are not detected in HER-2 low expressing OVCAR3 tumors after systemic delivery of HER-2 targeted-IONPs. Since HER-2 is expressed in a high percentage of ovarian cancers, the HER-2 targeted dual imaging modality IONPs have potential for the development of novel targeted imaging and therapeutic nanoparticles for ovarian cancer detection, targeted drug delivery, and image-guided therapy and surgery.
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Minati
authors.initials: M
authors.lastname: Satpathy
authors.forename: Liya
authors.initials: L
authors.lastname: Wang
authors.forename: Rafal
authors.initials: R
authors.lastname: Zielinski
authors.forename: Weiping
authors.initials: W
authors.lastname: Qian
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Lipowska
authors.forename: Jacek
authors.initials: J
authors.lastname: Capala
authors.forename: Gee Young
authors.initials: GY
authors.lastname: Lee
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Y Andrew
authors.initials: YA
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
authors.forename: Lily
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D005706:Gallbladder Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000556:secondary; D006801:Humans; D058185:Magnetite Nanoparticles; D051379:Mice; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D061848:Optical Imaging; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D012680:Sensitivity and Specificity
chemical_list: D058185:Magnetite Nanoparticles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins
keywords: HER-2 affibody; HER-2 targeted nanoparticles; MRI; NIR-830 dye; Optical imaging; orthotopic ovarian tumor model
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