title: Anti-HER2 antibody and ScFvEGFR-conjugated antifouling magnetic iron oxide nanoparticles for targeting and magnetic resonance imaging of breast cancer.
abstract: Antifouling magnetic iron oxide nanoparticles (IONPs) coated with block copolymer poly(ethylene oxide)-block-poly(γ-methacryloxypropyltrimethoxysilane) (PEO-b-PγMPS) were investigated for improving cell targeting by reducing nonspecific uptake. Conjugation of a HER2 antibody, Herceptin®, or a single chain fragment (ScFv) of antibody against epidermal growth factor receptor (ScFvEGFR) to PEO-b-PγMPS-coated IONPs resulted in HER2-targeted or EGFR-targeted IONPs (anti-HER2-IONPs or ScFvEGFR-IONPs). The anti-HER2-IONPs bound specifically to SK-BR-3, a HER2-overexpressing breast cancer cell line, but not to MDA-MB-231, a HER2-underexpressing cell line. On the other hand, the ScFvEGFR-IONPs showed strong reactivity with MDA-MB-231, an EGFR-positive human breast cancer cell line, but not with MDA-MB-453, an EGFR-negative human breast cancer cell line. Transmission electron microscopy revealed internalization of the receptor-targeted nanoparticles by the targeted cancer cells. In addition, both antibody-conjugated and non-antibody-conjugated IONPs showed reduced nonspecific uptake by RAW264.7 mouse macrophages in vitro. The developed IONPs showed a long blood circulation time (serum half-life 11.6 hours) in mice and low accumulation in both the liver and spleen. At 24 hours after systemic administration of ScFvEGFR-IONPs into mice bearing EGFR-positive breast cancer 4T1 mouse mammary tumors, magnetic resonance imaging revealed signal reduction in the tumor as a result of the accumulation of the targeted IONPs.
authors.affiliation: Department of Radiology and Imaging Sciences, Atlanta, GA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Chen
authors.forename: Liya
authors.initials: L
authors.lastname: Wang
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Yu
authors.forename: Weiping
authors.initials: W
authors.lastname: Qian
authors.forename: Diana
authors.initials: D
authors.lastname: Tiwari
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Lily
authors.initials: L
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible / Q000493:pharmacokinetics; D003287:Contrast Media / Q000138:chemical synthesis / Q000493:pharmacokinetics; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D057127:Single-Chain Antibodies / Q000187:drug effects / Q000493:pharmacokinetics*
chemical_list: D000911:Antibodies, Monoclonal; D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D066246:ErbB Receptors; D058185:Magnetite Nanoparticles; D018719:Erb-b2 Receptor Tyrosine Kinases; D057127:Single-Chain Antibodies
keywords: active targeting; antifouling; breast cancer; magnetic nanoparticles; magnetic resonance imaging