title: Theranostic nanoparticles carrying doxorubicin attenuate targeting ligand specific antibody responses following systemic delivery.
abstract: Understanding the effects of immune responses on targeted delivery of nanoparticles is important for clinical translations of new cancer imaging and therapeutic nanoparticles. In this study, we found that repeated administrations of magnetic iron oxide nanoparticles (IONPs) conjugated with mouse or human derived targeting ligands induced high levels of ligand specific antibody responses in normal and tumor bearing mice while injections of unconjugated mouse ligands were weakly immunogenic and induced a very low level of antibody response in mice. Mice that received intravenous injections of targeted and polyethylene glycol (PEG)-coated IONPs further increased the ligand specific antibody production due to differential uptake of PEG-coated nanoparticles by macrophages and dendritic cells. However, the production of ligand specific antibodies was markedly inhibited following systemic delivery of theranostic nanoparticles carrying a chemotherapy drug, doxorubicin. Targeted imaging and histological analysis revealed that lack of the ligand specific antibodies led to an increase in intratumoral delivery of targeted nanoparticles. Results of this study support the potential of further development of targeted theranostic nanoparticles for the treatment of human cancers.
authors.affiliation: 1. Departments of Surgery, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Emmy
authors.initials: E
authors.lastname: Yang
authors.affiliation: 1. Departments of Surgery, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Weiping
authors.initials: W
authors.lastname: Qian
authors.affiliation: 1. Departments of Surgery, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Zehong
authors.initials: Z
authors.lastname: Cao
authors.affiliation: 2. Departments of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: Liya
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1. Departments of Surgery, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Erica N
authors.initials: EN
authors.lastname: Bozeman
authors.affiliation: 1. Departments of Surgery, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Christina
authors.initials: C
authors.lastname: Ward
authors.affiliation: 3. Chengdu Women's and Children's Central Hospital, Chengdu, China;
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: 4. Departments of Pathology, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: Periasamy
authors.initials: P
authors.lastname: Selvaraj
authors.affiliation: 2. Departments of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Lipowska
authors.affiliation: 5. Ocean Nanotech, LLC, San Diego, CA 92126.
authors.forename: Y Andrew
authors.initials: YA
authors.lastname: Wang
authors.affiliation: 2. Departments of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
authors.affiliation: 1. Departments of Surgery, Emory University School of Medicine, Atlanta, GA 30322; ; 2. Departments of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: Lily
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000276:immunology* / Q000627:therapeutic use; D000917:Antibody Formation; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D004317:Doxorubicin / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D053758:Nanoparticles / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D004317:Doxorubicin
keywords: Targeting ligands; antibody; immune response; nanoparticle delivery.; nanoparticles; tumor imaging