Activation of Immune Responses Through the RIG-I Pathway Using TRITC-Dextran Encapsulated Nanoparticles

Hayeon Baek; Seung-Woo Yang; Min-Kyung Kim; Dongwoo Kim; Chaeyeon Lee; Seulki Kim; Yunseok Lee; Min Park; Han-Sung Hwang; Hyun-Jong Paik; Young-Sun Kang

doi:10.4110/in.2024.24.e44

Activation of Immune Responses Through the RIG-I Pathway Using TRITC-Dextran Encapsulated Nanoparticles

Immune Netw. 2024 Dec 24;24(6):e44. doi: 10.4110/in.2024.24.e44. eCollection 2024 Dec.

Authors

Hayeon Baek¹, Seung-Woo Yang^{2

3}, Min-Kyung Kim¹, Dongwoo Kim⁴, Chaeyeon Lee⁴, Seulki Kim⁵, Yunseok Lee⁶, Min Park¹, Han-Sung Hwang³, Hyun-Jong Paik⁴, Young-Sun Kang^{1

5}

Affiliations

¹ Department of KONKUK-KIST Biomedical Science & Technology, Konkuk University, Seoul 05029, Korea.
² Sanford Consortium for Regenerative Medicine, School of Medicine, University of California, San Diego, CA 92521, USA.
³ Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul 05029, Korea.
⁴ Department of Polymer Science and Engineering, Pusan National University, Busan 46241, Korea.
⁵ Department of Veterinary Pharmacology and Toxicology, Veterinary Science Research Institute, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.
⁶ Department of Animal Science and Technology, College of Sang-Huh Life Science, Konkuk University, Seoul 05029, Korea.

Abstract

Pathogen-associated molecular patterns (PAMPs) are highly conserved motifs originating from microorganisms that act as ligands for pattern recognition receptors (PRRs), which are crucial for defense against pathogens. Thus, PAMP-mimicking vaccines may induce potent immune activation and provide broad-spectrum protection against microbes. Dextran encapsulation can regulate the surface characteristics of nanoparticles (NPs) and induces their surface modification. To determine whether dextran-encapsulated NPs can be used to develop antiviral vaccines by mimicking viral PAMPs, we synthesized NPs in a cyclohexane inverse miniemulsion (Basic-NPs) and further encapsulated them with dextran or tetramethylrhodamine isothiocyanate (TRITC)-dextran (Dex-NPs or TDex-NPs). We hypothesized that these dextran encapsulated NPs could activate innate immunity through cell surface or cytosolic PRRs. In vitro and in vivo experiments were performed using RAW 264.7 and C57BL/6 mice to test different concentrations and routes of administration. Only TDex-NPs rapidly increased retinoic acid-inducible gene I (RIG-I) at 8 h and directly bound to it, producing 120-300 pg/ml of IFN-α via the ERK/NF-κB signaling pathway in both in vitro and in vivo models. The effect of TDex-NPs in mice was observed exclusively with footpad injections. Our findings suggest that TRITC-dextran encapsulated NPs exhibit surface properties for RIG-I binding, offering potential development as a novel antiviral and anticancer RIG-I agonist.

Keywords: Interferon-alpha; Nanoparticles; Pathogen-associated molecular pattern; Pathogen-associated molecular pattern molecules; Receptors, pattern recognition; Retinoic acid-inducible gene I.