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

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.

Thiol-Responsive Gold Nanodot Swarm with Glycol Chitosan for Photothermal Cancer Therapy

“…These changes originated from the different states of morphologies that were proven by transmission electron microscopic (TEM) images. The TEM images clearly showed the existence of the gold nanoparticles as black dots [ 17 , 18 , 19 , 20 , 21 ]. Figure 1 d displayed the assembly of sGNPs in AuNSw before the addition of mPEG-SH (left) and dispersed sGNPs after the addition of mPEG-SH (right).…”

“…The particle structure of AuNSw consisted of a GCP core with amine functional groups and superficial sGNPs via interactions between amine groups and sGNPs. These sGNPs assembled temporally due to their weak interactions with amine groups, and their SPR peak shifted to the NIR region due to the plasmon coupling effect [ 19 ]. We showed the morphology of AuNSw with assembled sGNPs and the corresponding SPR peak at the NIR region in Figure 1 .…”

Theranostic Platforms Based on Silica and Magnetic Nanoparticles Containing Quinacrine, Chitosan, Fluorophores, and Quantum Dots

“…Chitosan forms a porous coating on the nanoparticle surface, which is supported by the finding that the amount of fluorophore immobilized on the chitosan coating is much higher than the value predicted to be immobilized on a spherical particle of this size. In addition, the authors of [31,32] also showed that unmodified and modified glycol chitosan coatings both form pores. In this case, crosslinking from different acids probably produces different porosity and pore size values.…”

Research Progress of Photothermal Nanomaterials in Multimodal Tumor Therapy

“…These treatment deficiencies have inspired the development of new, precise, and more effective treatment strategies for tumors. For example, several emerging treatment methods, such as photodynamic therapy (PDT) ( 7 , 8 ), photothermal therapy (PTT) ( 9 , 10 ), and photoacoustic therapy ( 11 , 12 ) have improved or can potentially improve therapeutic outcomes. Among them, PTT is a new type of minimally invasive tumor light therapy that has developed rapidly in recent years.…”