Antigen-Free Radionuclide-Embedded Gold Nanoparticles for Dendritic Cell Maturation, Tracking, and Strong Antitumor Immunity

Abstract

Dendritic cell (DC)-based cancer immunotherapy requires efficient maturation of DCs and sensitive monitoring of DCs localized in the lymph nodes that activate T cells. This paper reports a robust and simple surface chemistry for highly sensitive and stable radionuclide-embedded gold nanoparticles (Poly-Y-RIe-AuNPs) prepared with oligotyrosine-modified AuNPs with additional Au shell formation as a promising positron emission tomography/computed tomography imaging agent. The multiple oligotyrosine binding sites modified on AuNPs provide excellent stability for conjugated radioisotopes by forming an Au shell. They can be heavily conjugated with radioisotope iodine, which enables sensitive tracking of DCs in the lymphatic system. More importantly, it is found that the maturation of DCs is possible solely with Poly-Y-RIe-AuNPs without any additional stimulus for DC maturation. DCs matured by Poly-Y-RIe-AuNPs induce antitumor immunity to cervical cancer comparable to that produced from DCs pulsated with tumor lysates. These results demonstrate that the peptide-based surface chemistry of Poly-Y-RIe-AuNPs is a simple and straightforward method to produce a highly sensitive and stable nuclear medicine imaging agent that also improves the efficiency of current antitumor immunotherapies.

Keywords: cancer immunotherapy; dendritic cells; lymphatic system; maturation; positron emission tomography; radionuclide-embedded gold nanoparticles.