Theragnostic Glycol Chitosan-Conjugated Gold Nanoparticles for Photoacoustic Imaging of Regional Lymph Nodes and Delivering Tumor Antigen to Lymph Nodes

• Type of Material: Article
• Authors: In-Cheol Sun, Korea Institute of Science and Technology; SeongHoon Jo, Korea Institute of Science and Technology; Diego Dumani, Universidad Costa Rica; Wan Su Yun, Korea Institute of Science and Technology; Hong Yeol Yoon, Korea Institute of Science and Technology; Dong-Kwon Lim, Korea University; Cheol-Hee Ahn, Seoul National University; Stanislav Emelianov, Emory University; Kwangmeyung Kim, Korea Institute of Science and Technology
• Language: English
• Date: 2021-07-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/nano11071700
• Title of Journal or Parent Work: Nanomaterials
• Volume: 11
• Issue: 7
• Grant/Funding Information: This research was funded by the KU-KIST Graduate School of Converging Science and Technology (Korea University) and the Intramural Research Program of KIST.
• Keywords: theragnostic gold nanoparticle; lymph node; immunotherapy; photoacoustic imaging; CT; Chemistry, Multidisciplinary; Materials Science; Nanoscience & Nanotechnology; Immunotherapy; Chemistry; Head; Science & Technology; Metastasis; ovalbumin; Materials Science, Multidisciplinary; glycol chitosan; Technology; Science & Technology - Other Topics; Physics; US; Physical Sciences; Physics, Applied; tumor antigen delivery; Cellular uptake
• Research Categories: Physics, Acoustics; Biology, Microbiology; Health Sciences, Immunology; Engineering, Biomedical

Abstract

Lymph node mapping is important in cancer immunotherapy because the morphology of lymph nodes is one of the crucial evaluation criteria of immune responses. We developed new theragnostic glycol‐chitosan‐coated gold nanoparticles (GC‐AuNPs), which highlighted lymph nodes in ultrasound‐guided photoacoustic (US/PA) imaging. Moreover, the ovalbumin epitope was conjugated GC‐AuNPs (OVA‐GC‐AuNPs) for delivering tumor antigen to lymph node resident macrophage. In vitro studies proved the vigorous endocytosis activity of J774A.1 macrophage and consequent strong photoacoustic signals from them. The macrophages also presented a tumor antigen when OVA‐GC‐AuNPs were used for cellular uptake. After the lingual injection of GC‐AuNPs into healthy mice, cervical lymph nodes were visible in a US/PA imaging system with high contrast. Three‐dimensional analysis of lymph nodes revealed that the accumulation of GC‐AuNPs in the lymph node increased as the post‐injection time passed. Histological analysis showed GC‐AuNPs or OVA‐GC‐AuNPs located in subcapsular and medullar sinuses where macrophages are abundant. Our new theragnostic GC‐AuNPs present a superior performance in US/PA imaging of lymph nodes without targeting moieties or complex surface modification. Simultaneously, GC‐AuNPs were able to deliver tumor antigens to cause macrophages to present the OVA epitope at targeted lymph nodes, which would be valuable for cancer immunotherapy.