Activation of Immune Responses Through the RIG-I Pathway Using TRITC-Dextran Encapsulated Nanoparticles
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초록
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.
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.
참고문헌 (95)
- Khan I, "Nanoparticles : properties, applications and toxicities", Arab J Chem, 12, pp.908~931 (2019)
- Khan S, "A review on nanotechnology : properties, applications, and mechanistic insights of cellular uptake mechanisms", J Mol Liq, 348, pp.118008~ (2022)
- Yao Y, "Nanoparticle-based drug delivery in cancer therapy and its role in overcoming drug resistance", Front Mol Biosci, 7, pp.193~ (2020)
- Liu Y, "Effects of engineered nanoparticles on the innate immune system", Semin Immunol, 34, pp.25~32 (2017)
- Aljabali AA, "Nanomaterials and their impact on the immune system", Int J Mol Sci, 24, pp.2008~ (2023)
- Zhao T, "Vaccine adjuvants : mechanisms and platforms", Signal Transduct Target Ther, 8, pp.283~ (2023)
- Zhou J, "Biomimetic nanotechnology toward personalized vaccines", Adv Mater, 32, pp.e1901255~ (2020)
- Peek LJ, "Nanotechnology in vaccine delivery", Adv Drug Deliv Rev, 60, pp.915~928 (2008)
- Kobayashi K, "Surface engineering of nanoparticles for therapeutic applications", Polym J, 46, pp.460~468 (2014)
- El-Sherbiny IM, "Janus nano-and microparticles as smart drug delivery systems", Curr Pharm Biotechnol, 17, pp.673~682 (2016)
- Li H, "Functionalized silica nanoparticles : classification, synthetic approaches and recent advances in adsorption applications", Nanoscale, 13, pp.15998~16016 (2021)
- Boraschi D, "Nanoparticles and innate immunity : new perspectives on host defence", Semin Immunol, 34, pp.33~51 (2017)
- Dobrovolskaia MA, "Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution", Mol Pharm, 5, pp.487~495 (2008)
- Liu J, "The interaction between nanoparticles and immune system : application in the treatment of inflammatory diseases", J Nanobiotechnology, 20, pp.127~ (2022)
- Bamberger D, "Surface modification of polysaccharide-based nanoparticles with PEG and dextran and the effects on immune cell binding and stimulatory characteristics", Mol Pharm, 14, pp.4403~4416 (2017)
- Saito T, "Differential recognition of double-stranded RNA by RIG-I-like receptors in antiviral immunity", J Exp Med, 205, pp.1523~1527 (2008)
- Rehwinkel J, "RIG-I-like receptors : their regulation and roles in RNA sensing", Nat Rev Immunol, 20, pp.537~551 (2020)
- Thoresen D, "The molecular mechanism of RIG-I activation and signaling", Immunol Rev, 304, pp.154~168 (2021)
- Kell AM, "RIG-I in RNA virus recognition", Virology, 479-480, pp.110~121 (2015)
- Iurescia S, "The innate immune signalling pathways : turning RIG-I sensor activation against cancer", Cancers(Basel), 12, pp.3158~ (2020)
- Yong HY, "RIG-I-like receptors as novel targets for pan-antivirals and vaccine adjuvants against emerging and re-emerging viral infections", Front Immunol, 9, pp.1379~ (2018)
- Hemann EA, "A small molecule RIG-I agonist serves as an adjuvant to induce broad multifaceted influenza virus vaccine immunity", J Immunol, 210, pp.1247~1256 (2023)
- Jiang Y, "Exploiting RIG-I-like receptor pathway for cancer immunotherapy", J Hematol Oncol, 16, pp.8~ (2023)
- Jacobson ME, "Structural optimization of polymeric carriers to enhance the immunostimulatory activity of molecularly defined RIG-I agonists", ACS Cent Sci, 6, pp.2008~2022 (2020)
- Vanpouille-Box C, "Pharmacological modulation of nucleic acid sensors-therapeutic potential and persisting obstacles", Nat Rev Drug Discov, 18, pp.845~867 (2019)
- Zillinger T, "Targeted nanoparticle delivery of bifunctional RIG-I agonists to pancreatic cancer", Mol Ther, 27, pp.491~492 (2019)
- Wright JF, "AAV vector manufacturing process design and scalability-Bending the trajectory to address vector-associated immunotoxicities", Mol Ther, 30, pp.2119~2121 (2022)
- Yoo YJ, "Nanoparticle-based delivery strategies of multifaceted immunomodulatory RNA for cancer immunotherapy", J Control Release, 343, pp.564~583 (2022)
- Angehrn Z, "Artificial intelligence and machine learning applied at the point of care", Front Pharmacol, 11, pp.759~ (2020)
- Carmona-Ribeiro AM, "Supramolecular nanostructures for vaccines", Biomimetics(Basel), 7, pp.6~ (2021)
- Kamaly N, "Degradable controlled-release polymers and polymeric nanoparticles : mechanisms of controlling drug release", Chem Rev, 116, pp.2602~2663 (2016)
- Hou X, "Lipid nanoparticles for mRNA delivery", Nat Rev Mater, 6, pp.1078~1094 (2021)
- Mehta M, "Lipid-based nanoparticles for drug", gene delivery : an overview of the production techniques and difficulties encountered in their industrial development, 2023, pp.3, 600~619
- Dilliard SA, "Passive, active and endogenous organ-targeted lipid and polymer nanoparticles for delivery of genetic drugs", Nat Rev Mater, 8, pp.282~300 (2023)
- Lokugamage MP, "Optimization of lipid nanoparticles for the delivery of nebulized therapeutic mRNA to the lungs", Nat Biomed Eng, 5, pp.1059~1068 (2021)
- Marx S, "RIG-I-induced innate antiviral immunity protects mice from lethal SARS-CoV-2 infection", Mol Ther Nucleic Acids, 27, pp.1225~1234 (2022)
- Wang-Bishop L, "Nanoparticle retinoic acid-inducible gene I agonist for cancer immunotherapy", ACS Nano, 18, pp.11631~11643 (2024)
- Cristóbal I, "A complex microRNA regulatory network may control the HCP5", UTP3, VAMP3 signaling axis, pp.Mol Ther, 2023[DOI]
- Carneiro BA, "Targeting apoptosis in cancer therapy", Nat Rev Clin Oncol, 17, pp.395~417 (2020)
- Lucy TT, "Serial passaging of RAW 264. 7 cells modulates intracellular AGE formation and downregulates RANKL-induced in vitro osteoclastogenesis", Int J Mol Sci, 23, pp.2371~ (2022)
- Kim KM, "Intestinal anti-inflammatory activity of Sasa quelpaertensis leaf extract by suppressing lipopolysaccharide-stimulated inflammatory mediators in intestinal epithelial Caco-2 cells co-cultured with RAW 264. 7 macrophage cells", Nutr Res Pract, 9, pp.3~10 (2015)
- Xian H, "Stratified ubiquitination of RIG-I creates robust immune response and induces selective gene expression", Sci Adv, 3, pp.e1701764~ (2017)
- Huang Z, "RIG-I contributes to dsDNA-induced innate immune activation in human brain microvascular endothelial cells", Mol Immunol, 152, pp.78~85 (2022)
- Plociennikowska A, "TLR3 activation by Zika virus stimulates inflammatory cytokine production which dampens the antiviral response induced by RIG-I-like receptors", J Virol, 95, pp.e01050-20~ (2021)
- Mohamed A, "Closely related reovirus lab strains induce opposite expression of RIG-I", IFN-dependent versus-independent host genes, via mechanisms of slow replication versus polymorphisms in dsRNA binding σ3 respectively, 2020, pp.16, e1008803~
- Minchin S, "Understanding biochemistry : structure and function of nucleic acids", Essays Biochem, 63, pp.433~456 (2019)
- van den Berg AIS, "Polymeric delivery systems for nucleic acid therapeutics : approaching the clinic", J Control Release, 331, pp.121~141 (2021)
- Palmer CR, "Environmentally triggerable retinoic acid-inducible gene I agonists using synthetic polymer overhangs", Bioconjug Chem, 29, pp.742~747 (2018)
- Sardone V, "Antisense oligonucleotide-based therapy for neuromuscular disease", Molecules, 22, pp.563~ (2017)
- Paunovska K, "Drug delivery systems for RNA therapeutics", Nat Rev Genet, 23, pp.265~280 (2022)
- Das M, "Nanoparticle delivery of RIG-I agonist enables effective and safe adjuvant therapy in pancreatic cancer", Mol Ther, 27, pp.507~517 (2019)
- Peng B, "Robust delivery of RIG-I agonists using extracellular vesicles for anti-cancer immunotherapy", J Extracell Vesicles, 11, pp.e12187~ (2022)
- Brisse M, "Comparative structure and function analysis of the RIG-I-like receptors : RIG-I and MDA5", Front Immunol, 10, pp.1586~ (2019)
- Onomoto K, "Regulation of RIG-I-like receptor-mediated signaling : interaction between host and viral factors", Cell Mol Immunol, 18, pp.539~555 (2021)
- Wu Q, "Dextran-coated superparamagnetic iron oxide nanoparticles activate the MAPK pathway in human primary monocyte cells", Mol Med Rep, 18, pp.564~570 (2018)
- Bharde AA, "Magnetic nanoparticles as mediators of ligand-free activation of EGFR signaling", PLoS One, 8, pp.e68879~ (2013)
- Maggi LB Jr, "ERK activation is required for double-stranded RNA-and virus-induced interleukin-1 expression by macrophages", J Biol Chem, 278, pp.16683~16689 (2003)
- Dou H, "The one-pot synthesis of dextran-based nanoparticles and their application in in-situ fabrication of dextran-magnetite nanocomposites", J Mater Sci Mater Med, 19, pp.2575~2580 (2008)
- Kawaguchi T, "Dextran-magnetite complex : conformation of dextran chains and stability of solution", J Mater Sci Mater Med, 12, pp.121~127 (2001)
- Priya S, "Polysaccharide-based nanofibers for pharmaceutical and biomedical applications : a review", Int J Biol Macromol, 218, pp.209~224 (2022)
- Luanda A, "Past, present and future of biomedical applications of dextran-based hydrogels : a review", Int J Biol Macromol, 228, pp.794~807 (2023)
- Hu Q, "Recent advances in dextran-based drug delivery systems : From fabrication strategies to applications", Carbohydr Polym, 264, pp.117999~ (2021)
- Wang S, "Acetalated dextran based nano-and microparticles : synthesis, fabrication, and therapeutic applications", Chem Commun(Camb), 57, pp.4212~4229 (2021)
- Tassa C, "Dextran-coated iron oxide nanoparticles : a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy", Acc Chem Res, 44, pp.842~852 (2011)
- Kunc F, "Polycarboxylated dextran as a multivalent linker : synthesis and target recognition of the antibody-nanoparticle bioconjugates in PBS and serum", Langmuir, 35, pp.4909~4917 (2019)
- Ahmad T, "Ni-Fe2O4 nanoparticles as contrast agents for magnetic resonance imaging", J Nanosci Nanotechnol, 11, pp.5645~5650 (2011)
- Lee H, "Thermally cross-linked superparamagnetic iron oxide nanoparticles : synthesis and application as a dual imaging probe for cancer in vivo", J Am Chem Soc, 129, pp.12739~12745 (2007)
- Moore CJ, "Controlling colloidal stability of silica nanoparticles during bioconjugation reactions with proteins and improving their longer-term stability, handling and storage", J Mater Chem B Mater Biol Med, 3, pp.2043~2055 (2015)
- Khan MS, "Advancements in dextran-based nanocarriers for treatment and imaging of breast cancer", Int J Pharm, 643, pp.123276~ (2023)
- Vocelle D, "Dextran functionalization enhances nanoparticle-mediated siRNA delivery and silencing", Technology(Singap), 4, pp.42~54 (2016)
- Dubois A, "Enhanced anti-HCV activity of interferon alpha 17 subtype", Virol J, 6, pp.70~ (2009)
- West AP, "TLR signalling augments macrophage bactericidal activity through mitochondrial ROS", Nature, 472, pp.476~480 (2011)
- Kawauchi Y, "Comparison of the carbohydrate preference of SIGNR1 as a phagocytic receptor with the preference as an adhesion molecule", Int Immunopharmacol, 19, pp.27~36 (2014)
- Rennick JJ, "Key principles and methods for studying the endocytosis of biological and nanoparticle therapeutics", Nat Nanotechnol, 16, pp.266~276 (2021)
- Antonio LC, "The amount of dextran in PLGA nanocarriers modulates protein corona and promotes cell membrane damage", J Mater Chem B Mater Biol Med, 10, pp.8282~8294 (2022)
- Berry CC, "Cell response to dextran-derivatised iron oxide nanoparticles post internalisation", Biomaterials, 25, pp.5405~5413 (2004)
- Wilhelm C, "Intracellular uptake of anionic superparamagnetic nanoparticles as a function of their surface coating", Biomaterials, 24, pp.1001~1011 (2003)
- Motta V, "NOD-like receptors : versatile cytosolic sentinels", Physiol Rev, 95, pp.149~178 (2015)
- Man SM, "Regulation of inflammasome activation", Immunol Rev, 265, pp.6~21 (2015)
- Sun L, "Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway", Science, 339, pp.786~791 (2013)
- Li S, "Cytosolic and nuclear recognition of virus and viral evasion", Mol Biomed, 2, pp.30~ (2021)
- Ramasundaram S, "Dextran sulfate nanocarriers : design, strategies and biomedical applications", Int J Mol Sci, 24, pp.355~ (2022)
- Pansailom N, "Surface modification : PEG", dextran encapsulation of SPIONs, 2017, pp.4, 6306~6310
- Zeini D, "Influence of lysine and TRITC conjugation on the size and structure of dextran nanoconjugates with potential for biomolecule delivery to neurons", ACS Appl Bio Mater, 4, pp.6832~6842 (2021)
- Thoresen DT, "A rapid RIG-I signaling relay mediates efficient antiviral response", Mol Cell, 83, pp.90~104 (2023)
- Burkart SS, "High-resolution kinetic characterization of the RIG-I-signaling pathway and the antiviral response", Life Sci Alliance, 6, pp.e202302059~ (2023)
- Jiang M, "Self-recognition of an inducible host lncRNA by RIG-I feedback restricts innate immune response", Cell, 173, pp.906~919 (2018)
- Murakami T, "Structural and functional changes in high-density lipoprotein induced by chemical modification", Biomater Sci, 3, pp.712~715 (2015)
- Gao S, "Dextran-coated nanoparticles as immunosensing platforms : Consideration of polyaldehyde density, nanoparticle size and functionality", Talanta, 247, pp.123549~ (2022)
- Mitchell MJ, "Engineering precision nanoparticles for drug delivery", Nat Rev Drug Discov, 20, pp.101~124 (2021)
- Chenthamara D, "Therapeutic efficacy of nanoparticles and routes of administration", Biomater Res, 23, pp.20~ (2019)
- Manolova V, "Nanoparticles target distinct dendritic cell populations according to their size", Eur J Immunol, 38, pp.1404~1413 (2008)
- Taback B, "Molecular lymphatic mapping of the sentinel lymph node", Am J Pathol, 161, pp.1153~1161 (2002)
- Chaney EJ, "Lymphatic biodistribution of polylactide nanoparticles", Mol Imaging, 9, pp.153~162 (2010)
- McLennan DN, "Subcutaneous drug delivery and the role of the lymphatics", Drug Discov Today Technol, 2, pp.89~96 (2005)
