International Journal of Nanomedicine (Jan 2022)
The Immune-Enhancing Properties of Hwanglyeonhaedok-Tang-Mediated Biosynthesized Gold Nanoparticles in Macrophages and Splenocytes
Abstract
Xiao-Jie Mi,1 Xing Yue Xu,1 Han Sol Choi,1 Hoon Kim,1 Ik Hyun Cho,2 Tae-Hoo Yi,1 Yeon-Ju Kim1 1Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si, 17104, Gyeonggi-do, Republic of Korea; 2Department of Science in Korean Medicine and Brain Korea 21 Plus Program, Graduate School, Kyung Hee University, Seoul, 02447, Republic of KoreaCorrespondence: Yeon-Ju Kim; Ik Hyun Cho Tel +82-31-201-5634Fax +82-31-204-8116Email [email protected]; [email protected]: 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.Methods: 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.Results: 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.Discussion: 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.Keywords: HHT, herb formula, green synthesis, AuNPs, immunostimulation