Radionuclide-embedded gold nanoparticles for enhanced dendritic cell-based cancer immunotherapy, sensitive and quantitative tracking of dendritic cells with PET and Cerenkov luminescence

Abstract

Radionuclide-embedded gold nanoparticles (RIe-AuNPs) were developed as a highly sensitive and stable nuclear and optical imaging agent for efficient dendritic cell (DC)-based immunotherapy and sensitive tracking of DC-migration to lymph nodes. The RIe-AuNPs were synthesized via simple and straightforward DNA-based radiolabeling chemistry and additional Au shell formation strategies, leading to high radiosensitivity and excellent in vivo stability. The RIe-AuNPs exert no adverse effects on the biological functions of DCs, and labeled DCs show strong antitumor immunity for lung cancer. Furthermore, the high radiosensitivity of the RIe-AuNPs allows for sensitive and long-term monitoring of DC migration to draining lymph nodes. The developed Cerenkov radiation-based optical imaging approach provides quantitative and sensitive results comparable with that of positron emission tomography imaging. These results highlight the strong potential of the RIe-AuNPs as a highly sensitive and stable nuclear and optical imaging platform for future bioimaging application such as cell tracking and tumor imaging. Gold-based imaging agents containing safely implanted radioisotopes can make it simpler to track dendritic cells in vivo. Dendritic cells (DCs) are a key part of the human immune system, where they patrol and signal against foreign invaders. Efforts to track DCs in vivo are often hampered by imaging agents that are unstable or give poor signals in the body. The research team from South Korea found that modifying gold nanoparticle with adenine-rich DNA strands enabled loading of large quantities of iodine radioisotopes. After coating the nanoparticles with a protective gold shell, the team used them to label DCs injected into live mice. The positron emission tomography (PET) permitted sensitive tracking of DCs in the draining lymph node, also an optical imaging modality based on Cerenkov luminescence showed sensitive imaging capability comparable with that of PET. Herein, we provide a simple and straightforward DNA-based radiolabeling chemistry and additional Au shell formation strategy to obtain radionuclide-embedded gold nanoparticles (RIe-AuNPs) with a high radiosensitivity and excellent in vivo stability. The migration of DCs labeled with RIe-AuNPs to draining lymph nodes was monitored very sensitively and for a long time. The biological function of DCs labeled with RIe-AuNP was not altered and it showed strong antitumor immunity. Because of densely conjugated radioisotopes in RIe-AuNPs, we could obtain strong Cerenkov optical signal comparable with that of positron emission tomography.