Theranostic Nanoparticles Carrying Doxorubicin Attenuate Targeting Ligand Specific Antibody Responses Following Systemic Delivery

• Type of Material: Article
• Authors: Emmy Yang, Emory University; Wei Qian, Emory University; Zehong Cao, Emory University; Liya Wang, Emory University; Erica Bozeman, Emory University; Christina Ward, Emory University; Bin Yang, Chengdu Women's and Children's Central Hospital; Periasamy Selvaraj, Emory University; Malgorzata Lipowska, Emory University; Y. Andrew Wang, Ocean Nanotech; Hui Mao, Emory University; Lily Yang, Emory University
• Language: English
• Date: 2015-01-01
• Publisher: Ivyspring International Publisher
• Publication Version: Final Published Version
• Copyright Statement: © Ivyspring International Publisher.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.7150/thno.10350
• Title of Journal or Parent Work: Theranostics
• ISSN: 1838-7640
• Volume: 5
• Issue: 1
• Start Page: 43
• End Page: 61
• Grant/Funding Information: Dr. Yang is supported in part by Nancy Panoz Chair of Surgery in Cancer Research Funds.; This research project was supported by the following research grants from the National Institute of Health: R01#CA133722 (Yang), U01#CA151810 (Yang and Mao), R01#CA154129A (Yang), SBIR Phase II HHSN261201200029C (Wang and Yang), and R01# CA138993 (Selvaraj).
• Keywords: BREAST-CANCER; Life Sciences & Biomedicine; immune response; THERAPY; DENDRITIC CELLS; antibody; nanoparticles; Science & Technology; Targeting ligands; T-CELL; Research & Experimental Medicine; tumor imaging; SILICA NANOPARTICLES; ANTIGEN PRESENTATION; IMMUNE-RESPONSES; IRON-OXIDE NANOPARTICLES; nanoparticle delivery; TUMOR-CELLS; IN-VIVO; Medicine, Research & Experimental
• Research Categories: Health Sciences, Radiology; Health Sciences, Medicine and Surgery

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.