Theranostics 2015; 5(1):43-61. doi:10.7150/thno.10350

Research Paper

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

Emmy Yang1*, Weiping Qian1*, Zehong Cao1, Liya Wang2, Erica N. Bozeman1, Christina Ward1, Bin Yang3, Periasamy Selvaraj4, Malgorzata Lipowska2, Y. Andrew Wang5, Hui Mao2✉, Lily Yang1,2✉

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.
3. Chengdu Women's and Children's Central Hospital, Chengdu, China;
4. Departments of Pathology, Emory University School of Medicine, Atlanta, GA 30322.
5. Ocean Nanotech, LLC, San Diego, CA 92126.
* Authors contributed equally to this study.

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Citation:
Yang E, Qian W, Cao Z, Wang L, Bozeman EN, Ward C, Yang B, Selvaraj P, Lipowska M, Wang YA, Mao H, Yang L. Theranostic Nanoparticles Carrying Doxorubicin Attenuate Targeting Ligand Specific Antibody Responses Following Systemic Delivery. Theranostics 2015; 5(1):43-61. doi:10.7150/thno.10350. Available from http://www.thno.org/v05p0043.htm

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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.

Keywords: Targeting ligands, nanoparticles, antibody, immune response, tumor imaging, nanoparticle delivery.