68Ga-labeled dendrimer-entrapped gold nanoparticles for PET/CT dual-modality imaging and immunotherapy of tumors.

Abstract

The design and fabrication of nanoplatforms with both nuclear medical imaging and therapeutic functions remain challenging in current precision nanomedicine. Herein, we report the design of a novel nanoplatform based on glucose-modified dendrimer-entrapped gold nanoparticles (Au DENPs) labeled with radionuclide 68Ga and incorporated with cytosine-guanine (CpG) oligonucleotide for positron emission tomography (PET)/computed tomography (CT) dual-mode imaging and immunotherapy of tumors. In this study, generation 5 poly(amidoamine) (PAMAM) dendrimers were first modified to have 8.2 DOTA and 7.3 polyethylene glycol with the other end functionalized with 2-amino-2-deoxy-D-glucose (DG) for each dendrimer, entrapped with Au NPs, and then radiolabeled with 68Ga through the DOTA chelation. The synthesized DG-Au DENPs have good cytocompatibility, targeting specificity toward cancer cells expressing glucose transporters, and the ability to be labeled by 68Ga with great labeling efficiency (≥85%) and stability (≥95%). After being loaded with CpG, the formed DG-Au DENPs/CpG polyplexes were proven to be used for tumor dual-mode PET/CT imaging and immunotherapy by effectively maturing dendritic cells to initiate a T cell-based antitumor immune response in vivo. Compared with the DG-free polyplexes, the developed DG-Au DENPs/CpG polyplexes show a much more sensitive imaging effect and better inhibition effect of tumors. These findings demonstrate a unique design of 68Ga-labeled DG-Au DENPs, a promising theranostic nanoplatform that may be extended to tackle different tumor types.

• Authors: Cai Li, Lingzhou Zhao, Liang Jia, Zhijun Ouyang, Yue Gao, Rui Guo, Shaoli Song, Xiangyang Shi, Xueyan Cao
• Journal: Journal of materials chemistry. B (J Mater Chem B) Vol. 10 Issue 19 Pg. 3648-3656 (05 18 2022) ISSN: 2050-7518 [Electronic] England
• PMID: 35451446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dendrimers
• Gallium Radioisotopes
• Gold
• Glucose

Topics

• Dendrimers
• Gallium Radioisotopes
• Glucose
• Gold
• Humans
• Immunotherapy
• Metal Nanoparticles
• Neoplasms (diagnostic imaging, pathology, therapy)
• Positron Emission Tomography Computed Tomography
• Tomography, X-Ray Computed (methods)