Systemic Responses to Targeted Nanoparticle Imaging and Theranostic Agents

L. Yang
Emory University School of Medicine, US

Keywords: nanoparticle, cancer detection,

Summary:

Targeted nanoparticle imaging and therapeutic agents hold great promise for the development of new approaches for cancer detection and effective therapy. For future clinical translation, it is important to consider potential responses of the human body to administrated nanoparticles. One of the major concerns is that repeated delivery of targeted nanoparticles may induce a strong immune response, which decreases the efficacy of the nanoparticles. Various targeting ligands that recognize cellular receptors highly expressed in tumor cells have been used for generating tumor targeted nanoparticles. However, immune responses against nanoparticles and their effects on tumor targeting and efficiency of tumor imaging and therapy are largely unclear. Enhanced phagocytosis by macrophages may shorten blood circulation time of the nanoparticles. Production of targeting ligand-specific antibodies can block the receptor-binding site and reduce the efficiency of targeted delivery of nanoparticles into tumors. To address this issue, we have examined innate and adaptive immune responses to targeted nanoparticles with different surface modifications and targeting ligands in Balb/c mice bearing mouse 4T1 mammary tumors or in normal mice. We found that conjugation of a targeting ligand onto magnetic iron oxide nanoparticles increased immunogenicity of the ligand. The surface coating of polyethylene glycol (PEG) further enhanced the level of the targeting ligand-specific antibody. Additionally, targeting ligands from a different species stimulated phagocytosis of the nanoparticles by macrophages and activated a higher level of antibody production. However, for targeted therapy using nanoparticles carrying a chemotherapy drug, antibody response may not raise concern since the antibody levels in the mice that received the targeted theranostic nanoparticles were significantly inhibited. Results of our study will provide important information for the design and development of the effective tumor targeted nanoparticles for future translation into clinic applications.