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.

Visualization of Macrophage Recruitment to Inflammation Lesions using Highly Sensitive and Stable Radionuclide-Embedded Gold Nanoparticles as a Nuclear Bio-Imaging Platform

“…Previously, we successfully established highly sensitive and stable imaging agents as a nuclear medicine imaging platform (RIe-AuNPs) 13. Briefly, 20 nm core gold nanoparticles (AuNPs) were first functionalized with thiolated adenine bases (A 10 ), which allow for radio-labeling of over 2700 radioactive iodine molecules (Na 124 I or Na 125 I) on each adenine-rich-DNA-modified gold nanoparticle (A 10 -AuNP) (Fig.…”

“…Recently, we have developed radioactive iodide-encapsulated gold nanoparticle probes (RIe-AuNPs) for a novel nuclear medicine imaging platform that features a simple and straightforward approach 13. As these imaging agents exhibit marked sensitivity and stability in living mice, they might facilitate the early detection of macrophage migration to inflamed lesions as well as the serial monitoring of systemic distribution to various organs in response to inflammation stimuli, with associated easy and rapid quantification based on computed tomography (CT) segmentation.…”

Tracking dendritic cell migration into lymph nodes by using a novel PET probe 18F-tetrafluoroborate for sodium/iodide symporter

“…Furthermore, PET imaging allows quantitative analysis. Recent studies have used 124 I for dose planning in radionuclide therapy and immune cell tracking studies [15, 29–31]. However, PET imaging of NIS by using 124 I also is associated with some drawbacks.…”

Molecular Imaging in Nanotechnology and Theranostics

“…Nanoparticle-based agents bring great new potential to this emerging modality, allowing for more specific imaging [96-98] and therapy [99-101], while active or passive targeting [102] can map receptors [103] or enzymes [104] of interest. As nanoparticles for PET imaging are translated to the clinic, CL will undoubtedly follow suit, providing additional, complementary information to the benefit of the patient.…”