Periodontitis is a chronic inflammatory disease characterized by a dysregulated interaction between the subgingival microbiota and the host immune response, leading to the accumulation of excessive inflammatory mediators and progressive tissue destruction. In this study, we first established a correlation between polyamine accumulation and periodontal inflammation by testing clinical samples of gingival crevicular fluid. To test the hypothesis that polyamine scavenging will benefit periodontitis treatment, we developed a polyamine-capturing hydrogel loaded with charge modified dodecyl sulfobutyl ether-β-cyclodextrin (SCDC12). The self-assembled SCDC12 nanoparticles effectively alleviated the cellular oxidative stress, improved cell viability, and inhibited the expression of proinflammatory factors by capturing polyamines in vitro. In addition, SCDC12 inhibited the growth of periodontal pathogens and biofilm formation. In a rat periodontitis model, SCDC12 hydrogel inhibited the expression of the rate-limiting enzyme in polyamine anabolism, downregulated the level of proinflammatory factors, and reduced local inflammatory response and alveolar bone loss. Our findings highlight SCDC12 as a promising polyamine scavenger, offering a novel therapeutic strategy for periodontitis treatment by restoring polyamine homeostasis.
AkhovaANesterovaLShumkovMTkachenkoA. 2021. Cadaverine biosynthesis contributes to decreased Escherichia coli susceptibility to antibiotics. Res Microbiol. 172(7–8):103881. https://doi.org/10.1016/j.resmic.2021.103881
2.
Alfonso GarcíaSLParada-SanchezMTArboleda ToroD. 2020. The phenotype of gingival fibroblasts and their potential use in advanced therapies. Eur J Cell Biol. 99(7):151123. https://doi.org/10.1016/j.ejcb.2020.151123
ArmalytėJ, et al. 2023. A polyamine acetyltransferase regulates the motility and biofilm formation of Acinetobacter baumannii. Nat Commun. 14(1):3531. https://doi.org/10.1038/s41467-023-39316-5
5.
BanerjiRKanojiyaPPatilASarojSD. 2021. Polyamines in the virulence of bacterial pathogens of respiratory tract. Mol Oral Microbiol. 36(1):1–11. https://doi.org/10.1111/omi.12315
6.
BattagliaVDeStefano ShieldsCMurray-StewartTCaseroRAJr.2014. Polyamine catabolism in carcinogenesis: potential targets for chemotherapy and chemoprevention. Amino Acids. 46(3):511–519. https://doi.org/10.1007/s00726-013-1529-6
7.
BekebredeAFKeijerJGerritsWJJBoerVCJ. 2020. The molecular and physiological effects of protein-derived polyamines in the intestine. Nutrients. 12(1):197. https://doi.org/10.3390/nu12010197
8.
BelambriSA, et al. 2018. NADPH oxidase activation in neutrophils: role of the phosphorylation of its subunits. Eur J Clin Invest. 48(Suppl 2):e12951. https://doi.org/10.1111/eci.12951
9.
BernabeE, et al. 2025. Trends in the global, regional, and national burden of oral conditions from 1990 to 2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 405(10482):897–910. https://doi.org/10.1016/s0140-6736(24)02811-3
ChiaTYZolpAMiskaJ. 2022. Polyamine immunometabolism: central regulators of inflammation, cancer and autoimmunity. Cells. 11(5):896. https://doi.org/10.3390/cells11050896
12.
CsomósK, et al. 2016. Protein cross-linking by chlorinated polyamines and transglutamylation stabilizes neutrophil extracellular traps. Cell Death Dis. 7(8):e2332. https://doi.org/10.1038/cddis.2016.200
13.
EbersoleJL, et al. 2017. The periodontal war: microbes and immunity. Periodontol 2000. 75(1):52–115. https://doi.org/10.1111/prd.12222
14.
FadistaJ, et al. 2021. Genetic regulation of spermine oxidase activity and cancer risk: a Mendelian randomization study. Sci Rep. 11(1):17463. https://doi.org/10.1038/s41598-021-97069-x
15.
GeckRC, et al. 2020. Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy. J Biol Chem. 295(19):6263–6277. https://doi.org/10.1074/jbc.ra119.012376
16.
GernerEWMeyskensFLJr.2009. Combination chemoprevention for colon cancer targeting polyamine synthesis and inflammation. Clin Cancer Res. 15(3):758–761. https://doi.org/10.1158/1078-0432.ccr-08-2235
17.
GuoS, et al. 2024. ROS-induced gingival fibroblast senescence: implications in exacerbating inflammatory responses in periodontal disease. Inflammation. 47(6):1918–1935. https://doi.org/10.1007/s10753-024-02014-5
18.
HajishengallisGChavakisTLambrisJD. 2020. Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy. Periodontol2000. 84(1):14–34. https://doi.org/10.1111/prd.12331
19.
HuangS, et al. 2020. Dextran methacrylate hydrogel microneedles loaded with doxorubicin and trametinib for continuous transdermal administration of melanoma. Carbohydr Polym. 246:116650. https://doi.org/10.1016/j.carbpol.2020.116650
JainV, et al. 2018. Reduction in polyamine catabolism leads to spermine-mediated airway epithelial injury and induces asthma features. Allergy. 73(10):2033–2045. https://doi.org/10.1111/all.13472
22.
JambhekarSSBreenP. 2016. Cyclodextrins in pharmaceutical formulations I: structure and physicochemical properties, formation of complexes, and types of complex. Drug Discov Today. 21(2):356–362. https://doi.org/10.1016/j.drudis.2015.11.017
LiaoCZhangCJinLYangY. 2020. IL-17 alters the mesenchymal stem cell niche towards osteogenesis in cooperation with osteocytes. J Cell Physiol. 235(5):4466-4480. http://doi.org/10.1002/jcp.29323
25.
LiJY, et al. 2019. IL-17 receptor signaling in osteoblasts/osteocytes mediates PTH-induced bone loss and enhances osteocytic RANKL production. J Bone Miner Res. 34(2):349–360. https://doi.org/10.1002/jbmr.3600
26.
LiW, et al. 2023. Disc regeneration by injectable fucoidan-methacrylated dextran hydrogels through mechanical transduction and macrophage immunomodulation. J Tissue Eng. 14:20417314231180050. https://doi.org/10.1177/20417314231180050
27.
LuchianIGoriucASanduDCovasaM. 2022. The role of matrix metalloproteinases (MMP-8, MMP-9, MMP-13) in periodontal and peri-implant pathological processes. Int J Mol Sci. 23(3):1806. https://doi.org/10.3390/ijms23031806
28.
LuoD, et al. 2024. The spermine oxidase/spermine axis coordinates ATG5-mediated autophagy to orchestrate renal senescence and fibrosis. Adv Sci (Weinh). 11(29):2306912. https://doi.org/10.1002/advs.202306912
29.
MariggiòMA, et al. 2004. In vitro effects of polyamines on polymorphonuclear cell apoptosis and implications in the pathogenesis of periodontal disease. Immunopharmacol Immunotoxicol. 26(1):93–101. https://doi.org/10.1081/iph-120029947
30.
Murray-StewartT, et al. 2018. Curcumin mediates polyamine metabolism and sensitizes gastrointestinal cancer cells to antitumor polyamine-targeted therapies. PLoS One. 13(8):e0202677. https://doi.org/10.1371/journal.pone.0202677
31.
NiuX, et al. 2018. Advances in the use of functional composites of β-cyclodextrin in electrochemical sensors. Microchim Acta. 185(7):328. https://doi.org/10.1007/s00604-018-2859-6
PanWWangQChenQ. 2019. The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci. 11(3):30. https://doi.org/10.1038/s41368-019-0064-z
34.
PardeshiCV, et al. 2023. Sulfobutylether-β-cyclodextrin: a functional biopolymer for drug delivery applications. Carbohydr Polym. 301(Pt B):120347. https://doi.org/10.1016/j.carbpol.2022.120347
35.
RashidMHKumarSPRajanRMamillapalliA. 2025. Salivary microbiota dysbiosis and elevated polyamine levels contribute to the severity of periodontal disease. BMC Oral Health. 25(1):2. https://doi.org/10.1186/s12903-024-05381-5
SakanakaA, et al. 2022. Fusobacterium nucleatum metabolically integrates commensals and pathogens in oral biofilms. mSystems. 7(4):e0017022. https://doi.org/10.1128/msystems.00170-22
38.
SczepanikFSC, et al. 2020. Periodontitis is an inflammatory disease of oxidative stress: we should treat it that way. Periodontol 2000. 84(1):45–68. https://doi.org/10.1111/prd.12342
UemuraTAkasakaYIkegayaH. 2020. Correlation of polyamines, acrolein-conjugated lysine and polyamine metabolic enzyme levels with age in human liver. Heliyon. 6(9):e05031. https://doi.org/10.1016/j.heliyon.2020.e05031
41.
XiaoE, et al. 2017. Diabetes enhances IL-17 expression and alters the oral microbiome to increase its pathogenicity. Cell Host Microbe. 22(1):120–128. https://doi.org/10.1016/j.chom.2017.06.014
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
