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Therefore, cell energy interference to alter macrophage functions has been proposed as a treatment for severe inflammatory diseases, including sepsis. In this study, targeting cell energy using BAM15 (a mitochondrial uncoupling agent) in human THP-1 and mouse RAW264.7 macrophages prominently interfered with M1 but not M2 polarization. Free BAM15 (BAM15) and BAM15-loaded PLGA particles (BAM15 particles) reduced the inflammatory response of M1 macrophages and enhanced the expression of M2 signature genes with the restoration of mitochondrial activity (extracellular flux analysis) in RAW264.7 cells. Furthermore, BAM15 particles but not BAM15 showed specific effects on the inflammatory response of macrophages but not neutrophils, and the particles were actively captured by splenic and liver macrophages in vivo. Administration of BAM15 and BAM15 particles attenuated the severity of sepsis in LPS-induced sepsis mice. Interestingly, BAM15 particles but not BAM15 alleviated LPS-induced liver injury by reducing hepatic inflammation. Our findings substantiate the superior efficacy of macrophage-targeted therapy using a BAM15 particle-delivery system and provide further support for clinical development as a potential therapy for severe inflammatory diseases.<\/jats:p>","DOI":"10.3390\/pharmaceutics15122695","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T11:43:16Z","timestamp":1701171796000},"page":"2695","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Polymeric Particle BAM15 Targeting Macrophages Attenuates the Severity of LPS-Induced Sepsis: A Proof of Concept for Specific Immune Cell-Targeted Therapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0928-1801","authenticated-orcid":false,"given":"Kanyarat","family":"Udompornpitak","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, 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Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107791","DOI":"10.1016\/j.intimp.2021.107791","article-title":"The roles of macrophage polarization in the host immune response to sepsis","volume":"96","author":"Chen","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1159\/000516780","article-title":"Metabolic Regulation of Macrophage Activation","volume":"14","author":"Kolliniati","year":"2022","journal-title":"J. Innate Immun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1209438","DOI":"10.3389\/fimmu.2023.1209438","article-title":"The role of macrophages polarization in sepsis-induced acute lung injury","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"888713","DOI":"10.3389\/fimmu.2022.888713","article-title":"Shaping Polarization of Tumor-Associated Macrophages in Cancer Immunotherapy","volume":"13","author":"Gao","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/s41573-022-00520-5","article-title":"Macrophages as tools and targets in cancer therapy","volume":"21","author":"Mantovani","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.it.2017.03.001","article-title":"Macrophage Immunometabolism: Where Are We (Going)?","volume":"38","author":"Menon","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, Y., Li, N., Zhang, X., and Horng, T. (2021). Mitochondrial metabolism regulates macrophage biology. J. Biol. Chem., 297.","DOI":"10.1016\/j.jbc.2021.100904"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Xu, L., Yan, X., Zhao, Y., Wang, J., Liu, B., Yu, S., Fu, J., Liu, Y., and Su, J. (2022). Macrophage Polarization Mediated by Mitochondrial Dysfunction Induces Adipose Tissue Inflammation in Obesity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169252"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Luo, R., Li, X., and Wang, D. (2022). Reprogramming Macrophage Metabolism and its Effect on NLRP3 Inflammasome Activation in Sepsis. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.917818"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.3389\/fimmu.2019.02461","article-title":"Pivotal Role of Mitochondria in Macrophage Response to Bacterial Pathogens","volume":"10","author":"Ramond","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1038\/s41467-020-16298-2","article-title":"Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice","volume":"11","author":"Alexopoulos","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s40170-021-00274-5","article-title":"Breast cancer growth and proliferation is suppressed by the mitochondrial targeted furazano[3,4-b]pyrazine BAM15","volume":"9","author":"Zunica","year":"2021","journal-title":"Cancer Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1159\/000516348","article-title":"BAM15, a Mitochondrial Uncoupling Agent, Attenuates Inflammation in the LPS Injection Mouse Model: An Adjunctive Anti-Inflammation on Macrophages and Hepatocytes","volume":"13","author":"Dang","year":"2021","journal-title":"J. Innate Immun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.addr.2019.12.001","article-title":"Drug delivery to macrophages: A review of targeting drugs and drug carriers to macrophages for inflammatory diseases","volume":"165","author":"He","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1080\/17425247.2020.1783237","article-title":"Drug delivery to macrophages: A review of nano-therapeutics targeted approach for inflammatory disorders and cancer","volume":"17","author":"Mukhtar","year":"2020","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Horvath, D., and Basler, M. (2023). PLGA Particles in Immunotherapy. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020615"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Loureiro, J.A., and Pereira, M.C. (2020). PLGA Based Drug Carrier and Pharmaceutical Applications: The Most Recent Advances. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12090903"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Khiewkamrop, P., Kaewraemruaen, C., Manipuntee, C., Saengruengrit, C., Insin, N., Leelahavanichkul, A., Kaewduangduen, W., Sonpoung, O., Ariya-Anandech, K., and Hirankarn, N. (2023). Immunosuppressive Polymeric Nanoparticles Targeting Dendritic Cells Alleviate Lupus Disease in Fcgr2b(-\/-) Mice by Mediating Antigen-Specific Immune Tolerance. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098313"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jcis.2018.03.008","article-title":"The combined magnetic field and iron oxide-PLGA composite particles: Effective protein antigen delivery and immune stimulation in dendritic cells","volume":"520","author":"Saengruengrit","year":"2018","journal-title":"J. Colloid Interface Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5985209","DOI":"10.1155\/2017\/5985209","article-title":"Role of Oxidative Stress and Mitochondrial Dysfunction in Sepsis and Potential Therapies","volume":"2017","author":"Mantzarlis","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.4266\/acc.2018.00157","article-title":"Role of Mitochondrial Oxidative Stress in Sepsis","volume":"33","author":"Nagar","year":"2018","journal-title":"Acute Crit. Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"708186","DOI":"10.3389\/fimmu.2021.708186","article-title":"Macrophages: The Good, the Bad, and the Gluttony","volume":"12","author":"Ross","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Saisorn, W., Phuengmaung, P., Issara-Amphorn, J., Makjaroen, J., Visitchanakun, P., Sae-Khow, K., Boonmee, A., Benjaskulluecha, S., Nita-Lazar, A., and Palaga, T. (2023). Less Severe Lipopolysaccharide-Induced Inflammation in Conditional mgmt-Deleted Mice with LysM-Cre System: The Loss of DNA Repair in Macrophages. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210139"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1026173","DOI":"10.3389\/fimmu.2022.1026173","article-title":"Nanomaterials targeting macrophages in sepsis: A promising approach for sepsis management","volume":"13","author":"Song","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.2174\/1381612829666230904150759","article-title":"Macrophage-targeted Nanomedicine for Sepsis: Diagnosis and Therapy","volume":"29","author":"Yang","year":"2023","journal-title":"Curr. Pharm. Des."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Dang, C.P., and Leelahavanichkul, A. (2020). Over-expression of miR-223 induces M2 macrophage through glycolysis alteration and attenuates LPS-induced sepsis mouse model, the cell-based therapy in sepsis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0236038"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"68","DOI":"10.4103\/2229-4708.103875","article-title":"Comparison of UV spectrophotometry and high performance liquid chromatography methods for the determination of repaglinide in tablets","volume":"3","author":"Dhole","year":"2012","journal-title":"Pharm. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"G966","DOI":"10.1152\/ajpgi.00337.2019","article-title":"Gut leakage enhances sepsis susceptibility in iron-overloaded \u03b2-thalassemia mice through macrophage hyperinflammatory responses","volume":"318","author":"Visitchanakun","year":"2020","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jim.2016.01.012","article-title":"The choice of phorbol 12-myristate 13-acetate differentiation protocol influences the response of THP-1 macrophages to a pro-inflammatory stimulus","volume":"430","author":"Lund","year":"2016","journal-title":"J. Immunol. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Genin, M., Clement, F., Fattaccioli, A., Raes, M., and Michiels, C. (2015). M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1546-9"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sae-Khow, K., Charoensappakit, A., Chiewchengchol, D., and Leelahavanichkul, A. (2022). High-Dose Intravenous Ascorbate in Sepsis, a Pro-Oxidant Enhanced Microbicidal Activity and the Effect on Neutrophil Functions. Biomedicines, 11.","DOI":"10.3390\/biomedicines11010051"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"607945","DOI":"10.3389\/fimmu.2020.607945","article-title":"Modulation of Immune Responses by Particle Size and Shape","volume":"11","author":"Baranov","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1007\/s11051-012-1221-x","article-title":"Quantitative cellular uptake of double fluorescent core-shelled model submicronic particles","volume":"14","author":"Leclerc","year":"2012","journal-title":"J. Nanoparticle Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.immuni.2016.10.010","article-title":"Functions of Murine Dendritic Cells","volume":"45","author":"Durai","year":"2016","journal-title":"Immunity"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1002\/hep.22167","article-title":"Dendritic cells are required for effective cross-presentation in the murine liver","volume":"47","author":"Plitas","year":"2008","journal-title":"Hepatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/cei.12907","article-title":"Critical roles of conventional dendritic cells in promoting T cell-dependent hepatitis through regulating natural killer T cells","volume":"188","author":"Wang","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1139832","DOI":"10.3389\/fpubh.2023.1139832","article-title":"Global, regional, and national incidence and mortality of neonatal sepsis and other neonatal infections, 1990\u20132019","volume":"11","author":"Li","year":"2023","journal-title":"Front. Public Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3389\/fphys.2015.00036","article-title":"Mitochondrial uncoupling proteins and energy metabolism","volume":"6","author":"Busiello","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"112471","DOI":"10.1016\/j.celrep.2023.112471","article-title":"The glycolysis\/HIF-1\u03b1 axis defines the inflammatory role of IL-4-primed macrophages","volume":"42","author":"Dang","year":"2023","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/cr.2015.68","article-title":"Metabolic reprogramming in macrophages and dendritic cells in innate immunity","volume":"25","author":"Kelly","year":"2015","journal-title":"Cell Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"936167","DOI":"10.3389\/fimmu.2022.936167","article-title":"Role of metabolic reprogramming in pro-inflammatory cytokine secretion from LPS or silica-activated macrophages","volume":"13","author":"Marrocco","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg Effect: How Does it Benefit Cancer Cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.3389\/fimmu.2019.01462","article-title":"The Metabolic Signature of Macrophage Responses","volume":"10","author":"Viola","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40364-020-00251-y","article-title":"Metabolic reprogramming in macrophage responses","volume":"9","author":"Liu","year":"2021","journal-title":"Biomark. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e152401","DOI":"10.1172\/JCI152401","article-title":"BAM15 treats mouse sepsis and kidney injury, linking mortality, mitochondrial DNA, tubule damage, and neutrophils","volume":"133","author":"Tsuji","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.coph.2009.04.008","article-title":"Anti-inflammatory and pro-inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity","volume":"9","author":"Sanjabi","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1021\/mp300559v","article-title":"Quantitative Detection of PLGA Nanoparticle Degradation in Tissues following Intravenous Administration","volume":"10","author":"Mohammad","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1159\/000335216","article-title":"Innate Immune Functions of Macrophage Subpopulations in the Spleen","volume":"4","author":"Haan","year":"2012","journal-title":"J. Innate Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1136\/gut.52.2.307","article-title":"Dendritic cells and immune regulation in the liver","volume":"52","author":"Lau","year":"2003","journal-title":"Gut"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Doroudian, M., Zanganeh, S., Abbasgholinejad, E., and Donnelly, S.C. (2023). Nanomedicine in Lung Cancer Immunotherapy. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1144653"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Gharavi, A.T., Hanjani, N.A., Movahed, E., and Doroudian, M. (2022). The role of macrophage subtypes and exosomes in immunomodulation. Cell. Mol. Biol. Lett., 27.","DOI":"10.1186\/s11658-022-00384-y"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"614","DOI":"10.3389\/fimmu.2014.00614","article-title":"Molecular mechanisms that influence the macrophage m1-m2 polarization balance","volume":"5","author":"Wang","year":"2014","journal-title":"Front Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lam, R.S., O\u2019Brien-Simpson, N.M., Holden, J.A., Lenzo, J.C., Fong, S.B., and Reynolds, E.C. (2016). Unprimed, M1 and M2 Macrophages Differentially Interact with Porphyromonas gingivalis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158629"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hiengrach, P., Visitchanakun, P., Tongchairawewat, P., Tangsirisatian, P., Jungteerapanich, T., Ritprajak, P., Wannigama, D.L., Tangtanatakul, P., and Leelahavanichkul, A. (2022). Sepsis Encephalopathy Is Partly Mediated by miR370-3p-Induced Mitochondrial Injury but Attenuated by BAM15 in Cecal Ligation and Puncture Sepsis Male Mice. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105445"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/12\/2695\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:32:35Z","timestamp":1760131955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/12\/2695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,28]]},"references-count":56,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["pharmaceutics15122695"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15122695","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,28]]}}}