Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Macrophage-targeted Nanomedicine for Sepsis: Diagnosis and Therapy

Author(s): Liyuan Yang, Xiaoli Lou, Shanshan Hao, Li Zhou and Yanqiang Hou*

Volume 29, Issue 26, 2023

Published on: 12 September, 2023

Page: [2036 - 2049] Pages: 14

DOI: 10.2174/1381612829666230904150759

Price: $65


Sepsis is a syndrome involving complex pathophysiological and biochemical dysregulation. Nanotechnology can improve our understanding of the pathophysiology of sepsis and contribute to the development of novel diagnostic and therapeutic strategies to further reduce the risk of sepsis. Macrophages play a key role in the progression of sepsis, thus, macrophage-associated pathological processes are important targets for both diagnostic and treatment of sepsis. In this paper, we reviewed efforts in the past decade of nanotechnologybased solutions for manipulate macrophages in sepsis diagnosis and management according to the type of nanomaterial. We addressed the latest progress of nanoparticles targeting macrophages for early sepsis detection. Additionally, we summarized the unique advantages of macrophage-targeted nanoparticles in the treatment of sepsis. These nanoparticles can improve the dysregulation of inflammatory response in sepsis by inhibiting the release of inflammatory factors and regulating macrophage apoptosis, activity and polarization. Finally, we present future opportunities as well as challenges of novel diagnostic and therapeutic strategies with the aim of accelerating the clinical translation of nanomedicine for sepsis treatment.

Keywords: Sepsis, macrophage, nanoparticle, diagnoses, nanomedicine, pathophysiological and biochemical dysregulation.

Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315(8): 801-10.
[] [PMID: 26903338]
Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the Global Burden of Disease Study. Lancet 2020; 395(10219): 200-11.
[] [PMID: 31954465]
Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically Ill patients with COVID-19 in Washington State. JAMA 2020; 323(16): 1612-4.
[] [PMID: 32191259]
Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020; 5(7): 811-8.
[] [PMID: 32219356]
Qiu P, Liu Y, Zhang J. Review: The role and mechanisms of macrophage autophagy in sepsis. Inflammation 2019; 42(1): 6-19.
[] [PMID: 30194660]
Chen X, Liu Y, Gao Y, Shou S, Chai Y. The roles of macrophage polarization in the host immune response to sepsis. Int Immunopharmacol 2021; 96: 107791.
[] [PMID: 34162154]
Mailänder V, Landfester K. Interaction of nanoparticles with cells. Biomacromolecules 2009; 10(9): 2379-400.
[] [PMID: 19637907]
Yildiz I, Shukla S, Steinmetz NF. Applications of viral nanoparticles in medicine. Curr Opin Biotechnol 2011; 22(6): 901-8.
[] [PMID: 21592772]
Riley RS, June CH, Langer R, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov 2019; 18(3): 175-96.
[] [PMID: 30622344]
Boraschi D, Italiani P, Palomba R, et al. Nanoparticles and innate immunity: New perspectives on host defence. Semin Immunol 2017; 34: 33-51.
[] [PMID: 28869063]
Pant A, Mackraj I, Govender T. Advances in sepsis diagnosis and management: A paradigm shift towards nanotechnology. J Biomed Sci 2021; 28(1): 6.
[] [PMID: 33413364]
Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol 2018; 233(9): 6425-40.
[] [PMID: 29319160]
Joffe AM, Bakalar MH, Fletcher DA. Macrophage phagocytosis assay with reconstituted target particles. Nat Protoc 2020; 15(7): 2230-46.
[] [PMID: 32561889]
Liu YC, Zou XB, Chai YF, Yao YM. Macrophage polarization in inflammatory diseases. Int J Biol Sci 2014; 10(5): 520-9.
[] [PMID: 24910531]
Barichello T, Generoso JS, Singer M, Dal-Pizzol F. Biomarkers for sepsis: More than just fever and leukocytosis-a narrative review. Crit Care 2022; 26(1): 14.
[] [PMID: 34991675]
Lee N, Yoo D, Ling D, Cho MH, Hyeon T, Cheon J. Iron oxide based nanoparticles for multimodal imaging and magnetoresponsive therapy. Chem Rev 2015; 115(19): 10637-89.
[] [PMID: 26250431]
Curcio A, Silva AKA, Cabana S, et al. Iron oxide nanoflowers @ CuS hybrids for cancer tri-therapy: Interplay of photothermal therapy, magnetic hyperthermia and photodynamic therapy. Theranostics 2019; 9(5): 1288-302.
[] [PMID: 30867831]
Wong R, Jian S, Yi W. Probing sepsis and sepsis-like conditions using untargeted SPIO nanoparticles. Annu Int Conf IEEE Eng Med Biol Soc 2010; 2010: 3053-6.
[] [PMID: 21095733]
Lee DY, Kang S, Lee Y, et al. PEGylated bilirubin-coated iron oxide nanoparticles as a biosensor for magnetic relaxation switching-based ROS detection in whole blood. Theranostics 2020; 10(5): 1997-2007.
[] [PMID: 32104497]
Nahrendorf M, Hoyer FF, Meerwaldt AE, et al. Imaging cardiovascular and lung macrophages with the positron emission tomography Sensor64 Cu-macrin in mice, rabbits, and pigs. Circ Cardiovasc Imaging 2020; 13(10): e010586.
[] [PMID: 33076700]
Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013; 369(9): 840-51.
[] [PMID: 23984731]
Hernandez-Beeftink T, Guillen-Guio B, Lorenzo-Salazar JM, et al. A genome-wide association study of survival in patients with sepsis. Crit Care 2022; 26(1): 341.
[] [PMID: 36335405]
Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017; 376(23): 2235-44.
[] [PMID: 28528569]
Namath A, Patterson AJ. Genetic polymorphisms in sepsis. Crit Care Clin 2009; 25(4): 835-56.
De Backer D, Cecconi M, Lipman J, et al. Challenges in the management of septic shock: A narrative review. Intensive Care Med 2019; 45(4): 420-33.
[] [PMID: 30741328]
Gotts JE, Matthay MA. Sepsis: Pathophysiology and clinical management. BMJ 2016; 353: i1585.
[] [PMID: 27217054]
Schultz MJ, Dunser MW, Dondorp AM, et al. Current challenges in the management of sepsis in ICUs in resource-poor settings and suggestions for the future. Intensive Care Med 2017; 43(5): 612-24.
[] [PMID: 28349179]
Wang X, Zhang Y, Kong H, et al. Novel mulberry silkworm cocoon-derived carbon dots and their anti-inflammatory properties. Artif Cells Nanomed Biotechnol 2020; 48(1): 68-76.
[] [PMID: 31852285]
Santos DS, Morais JAV, Vanderlei ÍAC, et al. Oral delivery of fish oil in oil-in-water nanoemulsion: Development, colloidal stability and modulatory effect on in vivo inflammatory induction in mice. Biomed Pharmacother 2021; 133110980.
[] [PMID: 33249282]
Cao H, Gao Y, Jia H, et al. Macrophage-membrane-camouflaged nonviral gene vectors for the treatment of multidrug-resistant bacterial sepsis. Nano Lett 2022; 22(19): 7882-91.
[] [PMID: 36169350]
Ye M, Zhao Y, Wang Y, et al. NAD(H)-loaded nanoparticles for efficient sepsis therapy via modulating immune and vascular homeostasis. Nat Nanotechnol 2022; 17(8): 880-90.
[] [PMID: 35668170]
Kühne M, Kretzer C, Lindemann H, et al. Biocompatible valproic acid-coupled nanoparticles attenuate lipopolysaccharide-induced inflammation. Int J Pharm 2021; 601120567.
[] [PMID: 33812975]
Ou A, Zhang J, Fang Y, et al. Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases. Acta Pharmacol Sin 2021; 42(11): 1913-20.
[] [PMID: 34561552]
Mathew AP, Rajendrakumar SK, Mohapatra A, et al. Hyaluronan-coated Prussian blue nanoparticles relieve LPS-induced peritonitis by suppressing oxidative species generation in tissue-resident macrophages. Biomater Sci 2022; 10(5): 1248-56.
[] [PMID: 35079755]
Xu MX, Ge CX, Qin YT, et al. Multicombination approach suppresses Listeria monocytogenes-induced septicemia-associated acute hepatic failure: The role of iRhom2 signaling. Adv Healthc Mater 2018; 7(17): 1800427.
[] [PMID: 29944201]
Rajendrakumar SK, Revuri V, Samidurai M, et al. Peroxidase-mimicking nanoassembly mitigates lipopolysaccharide-induced endotoxemia and cognitive damage in the brain by impeding inflammatory signaling in macrophages. Nano Lett 2018; 18(10): 6417-26.
[] [PMID: 30247915]
Luo J, Wang F, Sun F, et al. Targeted inhibition of FTO demethylase protects mice against LPS-induced septic shock by suppressing NLRP3 inflammasome. Front Immunol 2021; 12: 663295.
[] [PMID: 34017338]
Spence S, Greene MK, Fay F, et al. Targeting Siglecs with a sialic acid-decorated nanoparticle abrogates inflammation. Sci Transl Med 2015; 7(303): 303ra140.
[] [PMID: 26333936]
Hou X, Zhang X, Zhao W, et al. Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis. Nat Nanotechnol 2020; 15(1): 41-6.
[] [PMID: 31907443]
Casals E, Zeng M, Parra-Robert M, et al. Cerium oxide nanoparticles: Advances in biodistribution, toxicity, and preclinical exploration. Small 2020; 16(20): 1907322.
[] [PMID: 32329572]
Li YR, Zhu H. Nanoceria potently reduce superoxide fluxes from mitochondrial electron transport chain and plasma membrane NADPH oxidase in human macrophages. Mol Cell Biochem 2021; 476(12): 4461-70.
[] [PMID: 34478033]
Selvaraj V, Nepal N, Rogers S, et al. Cerium oxide nanoparticles inhibit lipopolysaccharide induced MAP kinase/NF-kB mediated severe sepsis. Data Brief 2015; 4: 105-15.
[] [PMID: 26217772]
Chen G, Xu Y. Biosynthesis of cerium oxide nanoparticles and their effect on lipopolysaccharide (LPS) induced sepsis mortality and associated hepatic dysfunction in male Sprague Dawley rats. Mater Sci Eng C 2018; 83: 148-53.
[] [PMID: 29208272]
Selvaraj V, Nepal N, Rogers S, et al. Lipopolysaccharide induced MAP kinase activation in RAW 264.7 cells attenuated by cerium oxide nanoparticles. Data Brief 2015; 4: 96-9.
[] [PMID: 26217770]
Selvaraj V, Manne NDPK, Arvapalli R, et al. Effect of cerium oxide nanoparticles on sepsis induced mortality and NF-κB signaling in cultured macrophages. Nanomedicine (Lond) 2015; 10(8): 1275-88.
[] [PMID: 25955124]
Selvaraj V, Nepal N, Rogers S, et al. Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles. Biomaterials 2015; 59: 160-71.
[] [PMID: 25968464]
Tang S, Zheng J. Antibacterial activity of silver nanoparticles: Structural effects. Adv Healthc Mater 2018; 7(13): 1701503.
[] [PMID: 29808627]
Yin H, Zhou M, Chen X, et al. Fructose-coated Ångstrom silver prevents sepsis by killing bacteria and attenuating bacterial toxin-induced injuries. Theranostics 2021; 11(17): 8152-71.
[] [PMID: 34373734]
Liu Y, Crawford BM, Vo-Dinh T. Gold nanoparticles-mediated photothermal therapy and immunotherapy. Immunotherapy 2018; 10(13): 1175-88.
[] [PMID: 30236026]
Taratummarat S, Sangphech N, Vu CTB, et al. Gold nanoparticles attenuates bacterial sepsis in cecal ligation and puncture mouse model through the induction of M2 macrophage polarization. BMC Microbiol 2018; 18(1): 85.
[] [PMID: 30119646]
Gao W, Wang L, Wang K, et al. Enhanced anti-inflammatory activity of peptide-gold nanoparticle hybrids upon cigarette smoke extract modification through TLR inhibition and autophagy induction. ACS Appl Mater Interfaces 2019; 11(36): 32706-19.
[] [PMID: 31411854]
Xu Y, Liu X, Li Y, Dou H, Liang H, Hou Y. SPION-MSCs enhance therapeutic efficacy in sepsis by regulating MSC-expressed TRAF1-dependent macrophage polarization. Stem Cell Res Ther 2021; 12(1): 531.
[] [PMID: 34627385]
Xu Y, Li Y, Liu X, et al. SPIONs enhances IL-10-producing macrophages to relieve sepsis via Cav1-Notch1/HES1-mediated autophagy. Int J Nanomedicine 2019; 14: 6779-97.
[] [PMID: 31692534]
Pan Y, Li J, Xia X, et al. β-glucan-coupled superparamagnetic iron oxide nanoparticles induce trained immunity to protect mice against sepsis Theranostics 2022; 12(2): 675-88.
[] [PMID: 34976207]
Soh M, Kang DW, Jeong HG, et al. Ceria-zirconia nanoparticles as an enhanced multi-antioxidant for sepsis treatment. Angew Chem Int Ed 2017; 56(38): 11399-403.
[] [PMID: 28643857]
Williams AT, Muller CR, Govender K, et al. Control of systemic inflammation through early nitric oxide supplementation with nitric oxide releasing nanoparticles. Free Radic Biol Med 2020; 161: 15-22.
[] [PMID: 33011274]
Feliciano CP, Tsuboi K, Suzuki K, Kimura H, Nagasaki Y. Long-term bioavailability of redox nanoparticles effectively reduces organ dysfunctions and death in whole-body irradiated mice. Biomaterials 2017; 129: 68-82.
[] [PMID: 28324866]
Wang X, Hao L, Bu HF, et al. Spherical nucleic acid targeting microRNA-99b enhances intestinal MFG-E8 gene expression and restores enterocyte migration in lipopolysaccharide-induced septic mice. Sci Rep 2016; 6(1): 31687.
[] [PMID: 27538453]
Dwivedi DJ, Toltl LJ, Swystun LL, et al. Prognostic utility and characterization of cell-free DNA in patients with severe sepsis. Crit Care 2012; 16(4): R151.
[] [PMID: 22889177]
Dawulieti J, Sun M, Zhao Y, et al. Treatment of severe sepsis with nanoparticulate cell-free DNA scavengers. Sci Adv 2020; 6(22): eaay7148.
[] [PMID: 32523983]
Shi C, Wang X, Wang L, et al. A nanotrap improves survival in severe sepsis by attenuating hyperinflammation. Nat Commun 2020; 11(1): 3384.
[] [PMID: 32636379]
Casey LM, Kakade S, Decker JT, et al. Cargo-less nanoparticles program innate immune cell responses to toll-like receptor activation. Biomaterials 2019; 218: 119333.
[] [PMID: 31301576]
Lasola JJM, Cottingham AL, Scotland BL, et al. Immunomodulatory nanoparticles mitigate macrophage inflammation via inhibition of PAMP interactions and lactate-mediated functional reprogramming of NF-κB and p38 MAPK. Pharmaceutics 2021; 13(11): 1841.
[] [PMID: 34834256]
Azadpour M, Farajollahi MM, Dariushnejad H, Varzi AM, Varezardi A, Barati M. Effects of synthetic silymarin-PLGA nanoparticles on M2 polarization and inflammatory cytokines in LPS-treated murine peritoneal macrophages. Iran J Basic Med Sci 2021; 24(10): 1446-54.
[] [PMID: 35096304]
Rashki S, Asgarpour K, Tarrahimofrad H, et al. Chitosan-based nanoparticles against bacterial infections. Carbohydr Polym 2021; 251117108.
[] [PMID: 33142645]
Torres-Rêgo M, Gláucia-Silva F, Rocha Soares KS, et al. Biodegradable cross-linked chitosan nanoparticles improve anti-Candida and anti-biofilm activity of TistH, a peptide identified in the venom gland of the Tityus stigmurus scorpion. Mater Sci Eng C 2019; 103: 109830.
[] [PMID: 31349502]
Mishra PR. An investigation on the approach to target lipopolysaccharide through polymeric capped nano-structured formulation for the management of sepsis. J Biomed Nanotechnol 2011; 7(1): 47-9.
[] [PMID: 21485797]
Ma L, Shen C, Gao L, et al. Anti-inflammatory activity of chitosan nanoparticles carrying NF-κB/p65 antisense oligonucleotide in RAW264.7 macropghage stimulated by lipopolysaccharide. Colloids Surf B Biointerfaces 2016; 142: 297-306.
[] [PMID: 26970817]
Cheng N, Zhang Y, Delaney MK, et al. Targeting Gα13-integrin interaction ameliorates systemic inflammation. Nat Commun 2021; 12(1): 3185.
[] [PMID: 34045461]
He H, Zheng N, Song Z, et al. Suppression of hepatic inflammation via systemic siRNA delivery by membrane-disruptive and endosomolytic helical polypeptide hybrid nanoparticles. ACS Nano 2016; 10(2): 1859-70.
[] [PMID: 26811880]
Sigalov AB. A novel ligand-independent peptide inhibitor of TREM-1 suppresses tumor growth in human lung cancer xenografts and prolongs survival of mice with lipopolysaccharide-induced septic shock. Int Immunopharmacol 2014; 21(1): 208-19.
[] [PMID: 24836682]
Chen YF, Chen GY, Chang CH, et al. TRAIL encapsulated to polypeptide-crosslinked nanogel exhibits increased anti-inflammatory activities in Klebsiella pneumoniae-induced sepsis treatment. Mater Sci Eng C 2019; 102: 85-95.
[] [PMID: 31147057]
Zhao H, Lv X, Huang J, et al. Two-phase releasing immune-stimulating composite orchestrates protection against microbial infections. Biomaterials 2021; 277: 121106.
[] [PMID: 34492581]
Chiu CH, Lee YT, Lin YC, et al. Bacterial membrane vesicles from induced by ceftazidime are more virulent than those induced by imipenem. Virulence 2020; 11(1): 145-58.
[] [PMID: 32043433]
Kunz N, Xia BT, Kalies KU, et al. Cell-derived nanoparticles are endogenous modulators of sepsis with therapeutic potential. Shock 2017; 48(3): 346-54.
[] [PMID: 28230708]
van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 2018; 19(4): 213-28.
[] [PMID: 29339798]
Bianchi ME, Crippa MP, Manfredi AA, Mezzapelle R, Rovere Querini P, Venereau E. High-mobility group box 1 protein orchestrates responses to tissue damage via inflammation, innate and adaptive immunity, and tissue repair. Immunol Rev 2017; 280(1): 74-82.
[] [PMID: 29027228]
Wang G, Jin S, Huang W, et al. LPS-induced macrophage HMGB1-loaded extracellular vesicles trigger hepatocyte pyroptosis by activating the NLRP3 inflammasome. Cell Death Discov 2021; 7(1): 337.
[] [PMID: 34743181]
Ding L, Zhou W, Zhang J, et al. Calming egress of inflammatory monocytes and related septic shock by therapeutic CCR2 silencing using macrophage-derived extracellular vesicles. Nanoscale 2022; 14(13): 4935-45.
[] [PMID: 35225315]
Park KS, Svennerholm K, Shelke GV, et al. Mesenchymal stromal cell-derived nanovesicles ameliorate bacterial outer membrane vesicle-induced sepsis via IL-10. Stem Cell Res Ther 2019; 10(1): 231.
[] [PMID: 31370884]
Ma J, Jiang L, Liu G. Cell membrane-coated nanoparticles for the treatment of bacterial infection. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2022; 14(5): e1825.
[] [PMID: 35725897]
Du X, Zhang M, Zhou H, et al. Decoy nanozymes enable multitarget blockade of proinflammatory cascades for the treatment of multi-drug-resistant bacterial sepsis. Research 2022.
[]] [PMID: 36258843]
Shen S, Han F, Yuan A, et al. Engineered nanoparticles disguised as macrophages for trapping lipopolysaccharide and preventing endotoxemia. Biomaterials 2019; 189: 60-8.
[] [PMID: 30388590]
Molinaro R, Pastò A, Corbo C, et al. Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages. Nanoscale 2019; 11(28): 13576-86.
[] [PMID: 31290914]
Thamphiwatana S, Angsantikul P, Escajadillo T, et al. Macrophage-like nanoparticles concurrently absorbing endotoxins and proinflammatory cytokines for sepsis management. Proc Natl Acad Sci USA 2017; 114(43): 11488-93.
[] [PMID: 29073076]
Wu B, Lin L, Zhou F, Wang X. Precise engineering of neutrophil membrane coated with polymeric nanoparticles concurrently absorbing of proinflammatory cytokines and endotoxins for management of sepsis. Bioprocess Biosyst Eng 2020; 43(11): 2065-74.
[] [PMID: 32583175]
Koo J, Escajadillo T, Zhang L, Nizet V, Lawrence SM. Erythrocyte-coated nanoparticles block cytotoxic effects of group B Streptococcus β-hemolysin/cytolysin. Front Pediatr 2019; 7: 410.
[] [PMID: 31737584]
Liu J, Ding H, Zhao M, et al. Functionalized erythrocyte membrane-coated nanoparticles for the treatment of Klebsiella pneumoniae-induced sepsis. Front Microbiol 2022; 13: 901979.
[] [PMID: 35783411]
Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021. Intensive Care Med 2021; 47(11): 1181-247.
[] [PMID: 34599691]
Medzhitov R. Origin and physiological roles of inflammation. Nature 2008; 454(7203): 428-35.
[] [PMID: 18650913]
Karami A, Xie Z, Zhang J, et al. Insights into the antimicrobial mechanism of Ag and I incorporated ZnO nanoparticle derivatives under visible light. Mater Sci Eng C 2020; 107110220.
[] [PMID: 31761246]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy