The Immune-Enhancing Properties of Hwanglyeonhaedok-Tang-Mediated Biosynthesized Gold Nanoparticles in Macrophages and Splenocytes

• Published in: International journal of nanomedicine Vol. 17; pp. 477 - 494
• Main Authors: Mi, Xiao-Jie, Xu, Xing Yue, Choi, Han Sol, Kim, Hoon, Cho, Ik Hyun, Yi, Tae-Hoo, Kim, Yeon-Ju
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2022; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Analysis; Animals; aunps; Biological activity; Chinese medicine; Cytokines; Enzyme-linked immunosorbent assay; Flavonoids; Gold; green synthesis; herb formula; hht; immunostimulation; Immunotherapy; Lipopolysaccharides; Macrophages; Medicine, Botanic; Medicine, Herbal; Metal Nanoparticles; Mice; Mice, Inbred ICR; Microscopy; Nanoparticles; Nanotechnology; NF-kappa B; Nitric oxide; Original Research; Pathogens; Spleen; Toxicity; Tumor necrosis factor-TNF; South Korea; Japan; China; United States > US; herb formula; green synthesis; HHT; AuNPs; immunostimulation
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S338334

Despite great advances in the field of immunotherapy, there is still a need for novel and effective immunostimulants to overcome challenges, such as instability and autoinflammatory toxicity, associated with conventional immunostimulants. Nanotechnology provides the possibility to overcome these challenges. The well-known classical Chinese formula, Hwanglyeonhaedok-tang (HHT) has been widely used to treat immune-related diseases in clinical practice. We developed novel gold nanoparticles (AuNPs) utilizing one-pot synthesis with the herbal formula-HHT. The optimal conditions for HHT-AuNP biosynthesis were established, and physicochemical properties of the optimized HHT-AuNPs were identified using various spectrometric and microscopic techniques. Bio-TEM analysis revealed that HHT-AuNPs were highly engulfed within RAW264.7 cells without inducing cytotoxicity. The effect of HHT-AuNPs on immunostimulatory activity was evaluated in innate and adaptive immune cells (RAW264.7 macrophages and ICR mice splenocytes) using qRT-PCR, immunoblotting, and ELISA. The HHT-AuNPs remarkably increased the nitric oxide (NO) and immune-related cytokines production by activating the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways in RAW264.7 cells. Furthermore, HHT-AuNPs exerted immunostimulatory effects on mouse splenocytes by priming T/B-cells and macrophages. The present study is the first to demonstrate that HHT-AuNPs could be utilized as immunostimulators to activate both innate and adaptive immune systems. These results provide a foundation for the application of traditional Chinese medicinal formulae in the field of nanomedicine.