CoChat
Sign Up
Cited by 48Endodontics and Root Canal TreatmentsPhotodynamic Therapy Research StudiesNanoplatforms for cancer theranostics

Photodynamic and nitric oxide therapy-based synergistic antimicrobial nanoplatform: an advanced root canal irrigation system for endodontic bacterial infections

Open access
Zeng, Youyun, Hu, Xiangyu, Cai, Zhibin, Qiu, Dongchao, Ran, Ying, Ding, Yiqin, Shi, Jiayi, Cai, Xiaojun +1 more·2024·Journal of Nanobiotechnology
DOI 10.1186/s12951-024-02483-8PMC PMC11059741
Open this paper in CoChat — free account

Abstract

Background: The main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects to shorten disease duration. Conventional root canal irrigants are limited in their efficacy and are associated with several side effects. This study introduces a synergistic therapy based on nitric oxide (NO) and antimicrobial photodynamic therapy (aPDT) for the treatment of apical periodontitis. Results: This research developed a multifunctional nanoparticle, CGP, utilizing guanidinylated poly (ethylene glycol)-poly (ε-Caprolactone) polymer as a carrier, internally loaded with the photosensitizer chlorin e6. During root canal irrigation, the guanidino groups on the surface of CGP enabled effective biofilm penetration. These groups undergo oxidation by hydrogen peroxide in the aPDT process, triggering the release of NO without hindering the production of singlet oxygen. The generated NO significantly enhanced the antimicrobial capability and biofilm eradication efficacy of aPDT. Furthermore, CGP not only outperforms conventional aPDT in eradicating biofilms but also effectively promotes the repair of alveolar bone defects post-eradication. Importantly, our findings reveal that CGP exhibits significantly higher biosafety compared to sodium hypochlorite, alongside superior therapeutic efficacy in a rat model of apical periodontitis. Conclusions: This study demonstrates that CGP, an effective root irrigation system based on aPDT and NO, has a promising application in root canal therapy.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s12951-024-02483-8

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Enzymolysis- and photothermal-mediated nanoplatforms have been developed to degrade extracellular polymeric substances and enhance biofilm penetration.

    “enzymolysis- and photothermal-mediated nanoplatforms have been developed to degrade extracellular polymeric substances and enhance biofilm penetration”

    From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [70]

    The Results and discussion section ('Bacterial association and biofilm permeation of CGP'; page unavailable) reports that the CGP nanoplatform penetrated biofilms more effectively than free Ce6. The paper describes guanidinylation and photodynamic/nitric oxide therapy, not enzymolysis or photothermal action, and does not report degradation of extracellular polymeric substances. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Photodynamic and nitric oxide therapy-based synergistic systems have been proposed as advanced root canal irrigation strategies for endodontic bacterial infections.

    “photodynamic and nitric oxide therapy-based synergistic systems have been proposed as advanced root canal irrigation strategies for endodontic bacterial infections.69,70”

    From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [70]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 57 · Cited by 48

Research works printed but not linked: 58

  1. [1]Kakehashi S Stanley HR Fitzgerald RJ The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats Oral Surg Oral Med Oral Pathol 1965 20 340 349 10.1016/0030-4220(65)90166-0 14342926 · DOI
  2. [2]Shah AC Leong KK Lee MK Allareddy V Outcomes of hospitalizations attributed to periapical abscess from 2000 to 2008: a longitudinal trend analysis J Endod 2013 39 1104 1110 10.1016/j.joen.2013.04.042 23953280 · DOI
  3. [3]Tiburcio-Machado CS Michelon C Zanatta FB Gomes MS Marin JA Bier CA The global prevalence of apical periodontitis: a systematic review and meta-analysis Int Endod J 2021 54 712 735 10.1111/iej.13467 33378579 · DOI
  4. [4]Persoon IF Ozok AR Definitions and epidemiology of endodontic infections Curr Oral Health Rep 2017 4 278 285 10.1007/s40496-017-0161-z 29201596 PMC5688219 · DOI
  5. [5]Distel JW Hatton JF Gillespie MJ Biofilm formation in medicated root canals J Endod 2002 28 689 693 10.1097/00004770-200210000-00003 12398165 · DOI
  6. [6]Mah TF Pitts B Pellock B Walker GC Stewart PS O'Toole GA A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance Nature 2003 426 306 310 10.1038/nature02122 14628055 · DOI
  7. [7]Zehnder M Root canal irrigants J Endod 2006 32 389 398 10.1016/j.joen.2005.09.014 16631834 · DOI
  8. [8]Al-Sebaei MO Halabi OA El-Hakim IE Sodium hypochlorite accident resulting in life-threatening airway obstruction during root canal treatment: a case report Clin Cosmet Investig Dent 2015 7 41 44 10.2147/CCIDE.S79436 25767406 PMC4354614 · DOI
  9. [9]Ortiz-Alves T Diaz-Sanchez R Gutierrez-Perez JL Gonzalez-Martin M Serrera-Figallo MA Torres-Lagares D Bone necrosis as a complication of sodium hypochlorite extrusion. A case report J Clin Exp Dent 2022 14 e885 889 10.4317/jced.59862 36320668 PMC9617265 · DOI
  10. [10]Xu R Guo D Zhou X Sun J Zhou Y Fan Y Zhou X Wan M Du W Zheng L Disturbed bone remodelling activity varies in different stages of experimental, gradually progressive apical periodontitis in rats Int J Oral Sci 2019 11 27 10.1038/s41368-019-0058-x 31451690 PMC6802676 · DOI
  11. [11]Xiao F Cao B Wang C Guo X Li M Xing D Hu X Pathogen-specific polymeric antimicrobials with significant membrane disruption and enhanced photodynamic damage to inhibit highly opportunistic bacteria ACS Nano 2019 13 1511 1525 10.1021/acsnano.8b07251 30632740 · DOI
  12. [12]Wang D Niu L Qiao ZY Cheng DB Wang J Zhong Y Bai F Wang H Fan H Synthesis of self-assembled porphyrin nanoparticle photosensitizers ACS Nano 2018 12 3796 3803 10.1021/acsnano.8b01010 29611423 · DOI
  13. [13]Zhu J Tian J Yang C Chen J Wu L Fan M Cai X L-Arg-rich amphiphilic dendritic peptide as a versatile NO donor for NO/photodynamic synergistic treatment of bacterial infections and promoting wound healing Small 2021 17 e2101495 10.1002/smll.202101495 34213822 · DOI
  14. [14]Carrinho PM Andreani DIK Morete VA Iseri S Navarro RS Villaverde AB A study on the macroscopic morphometry of the lesion area on diabetic ulcers in humans treated with photodynamic therapy using two methods of measurement Photomed Laser Surg 2018 36 44 50 10.1089/pho.2017.4305 29023192 · DOI
  15. [15]de Vasconcelos Catao MH Nonaka CF de Albuquerque Jr RL de BentoOliveira Costa PMR Effects of red laser, infrared, photodynamic therapy, and green LED on the healing process of third-degree burns: clinical and histological study in rats Lasers Med Sci 2015 30 421 428 10.1007/s10103-014-1687-0 25391372 · DOI
  16. [16]Gong J Park H Lee J Seo H Lee S Effect of photodynamic therapy on multispecies biofilms, including Streptococcus mutans, Lactobacillus casei, and Candida albicans Photobiomodul Photomed Laser Surg 2019 37 282 287 31084564
  17. [17]Wan SS Zeng JY Cheng H Zhang XZ ROS-induced NO generation for gas therapy and sensitizing photodynamic therapy of tumor Biomaterials 2018 185 51 62 10.1016/j.biomaterials.2018.09.004 30218836 · DOI
  18. [18]Xiu W Gan S Wen Q Qiu Q Dai S Dong H Li Q Yuwen L Weng L Teng Z Biofilm microenvironment-responsive nanotheranostics for dual-mode imaging and hypoxia-relief-enhanced photodynamic therapy of bacterial infections Research (Wash D C) 2020 2020 9426453 32377640 PMC7128073
  19. [19]Cao H Zhong S Wang Q Chen C Tian J Zhang W Enhanced photodynamic therapy based on an amphiphilic branched copolymer with pendant vinyl groups for simultaneous GSH depletion and Ce6 release J Mater Chem B 2020 8 478 483 10.1039/C9TB02120E 31834340 · DOI
  20. [20]Sun X Sun J Lv J Dong B Liu M Liu J Sun L Zhang G Zhang L Huang G Ce6-C6-TPZ co-loaded albumin nanoparticles for synergistic combined PDT-chemotherapy of cancer J Mater Chem B 2019 7 5797 5807 10.1039/C9TB01346F 31483422 · DOI
  21. [21]Liu HD Ren MX Li Y Zhang RT Ma NF Li TL Jiang WK Zhou Z Yao XW Liu ZY Yang M Melatonin alleviates hydrogen peroxide induced oxidative damage in MC3T3-E1 cells and promotes osteogenesis by activating SIRT1 Free Radic Res 2022 56 63 76 10.1080/10715762.2022.2037580 35109721 · DOI
  22. [22]Sheppard AJ Barfield AM Barton S Dong Y Understanding reactive oxygen species in bone regeneration: a glance at potential therapeutics and bioengineering applications Front Bioeng Biotechnol 2022 10 836764 10.3389/fbioe.2022.836764 35198545 PMC8859442 · DOI
  23. [23]Zhang J Guo H Liu M Tang K Li S Fang Q Du H Zhou X Lin X Yang Y Recent design strategies for boosting chemodynamic therapy of bacterial infections Exploration 2023 2023 20230087 PMC11022619 38855616
  24. [24]Liu R Peng Y Lu L Peng S Chen T Zhan M Near-infrared light-triggered nano-prodrug for cancer gas therapy J Nanobiotechnol 2021 19 443 10.1186/s12951-021-01078-x PMC8697457 34949202 · DOI
  25. [25]Yang Z Chen H Recent deveolpment of multifunctional responsive gas-releasing nanoplatforms for tumor therapeutic application Nano Res 2023 16 3924 3938 10.1007/s12274-022-4473-5 · DOI
  26. [26]Opoku-Damoah Y Zhang R Ta HT Xu ZP Therapeutic gas-releasing nanomedicines with controlled release: advances and perspectives Exploration (Beijing) 2022 2 20210181 10.1002/EXP.20210181 37325503 PMC10190986 · DOI
  27. [27]Backlund CJ Sergesketter AR Offenbacher S Schoenfisch MH Antibacterial efficacy of exogenous nitric oxide on periodontal pathogens J Dent Res 2014 93 1089 1094 10.1177/0022034514529974 25139363 PMC4293763 · DOI
  28. [28]Barui AK Nethi SK Patra CR Investigation of the role of nitric oxide driven angiogenesis by zinc oxide nanoflowers J Mater Chem B 2017 5 3391 3403 10.1039/C6TB03323G 32264405 · DOI
  29. [29]Qian Y Chug MK Brisbois EJ Nitric oxide-releasing silicone oil with tunable payload for antibacterial applications ACS Appl Bio Mater 2022 5 3396 3404 10.1021/acsabm.2c00358 35792809 · DOI
  30. [30]Lv X Jiang J Ren J Li H Yang D Song X Hu Y Wang W Dong X Nitric oxide-assisted photodynamic therapy for enhanced penetration and hypoxic bacterial biofilm elimination Adv Healthc Mater 2023 12 e2302031 10.1002/adhm.202302031 37515529 · DOI
  31. [31]Li G Yu S Xue W Ma D Zhang W Chitosan-graft-PAMAM loading nitric oxide for efficient antibacterial application Chem Eng J 2018 347 923 931 10.1016/j.cej.2018.04.159 · DOI
  32. [32]Saura M Tarin C Zaragoza C Recent insights into the implication of nitric oxide in osteoblast differentiation and proliferation during bone development Sci World J 2010 10 624 632 10.1100/tsw.2010.58 PMC5763674 20419275 · DOI
  33. [33]Won JE Kim WJ Shim JS Ryu JJ Guided bone regeneration with a nitric-oxide releasing polymer inducing angiogenesis and osteogenesis in critical-sized bone defects Macromol Biosci 2022 22 e2200162 10.1002/mabi.202200162 35895972 · DOI
  34. [34]Yasuhara R Suzawa T Miyamoto Y Wang X Takami M Yamada A Kamijo R Nitric oxide in pulp cell growth, differentiation, and mineralization J Dent Res 2007 86 163 168 10.1177/154405910708600211 17251517 · DOI
  35. [35]Izawa H Kinai M Ifuku S Morimoto M Saimoto H Guanidinylated chitosan inspired by arginine-rich cell-penetrating peptides Int J Biol Macromol 2019 125 901 905 10.1016/j.ijbiomac.2018.12.138 30572038 · DOI
  36. [36]Khan NF Nakamura H Izawa H Ifuku S Kadowaki D Otagiri M Anraku M Evaluation of the safety and gastrointestinal migration of guanidinylated chitosan after oral administration to rats J Funct Biomater 2023 14 340 10.3390/jfb14070340 37504835 PMC10381351 · DOI
  37. [37]Andreev K Bianchi C Laursen JS Citterio L Hein-Kristensen L Gram L Kuzmenko I Olsen CA Gidalevitz D Guanidino groups greatly enhance the action of antimicrobial peptidomimetics against bacterial cytoplasmic membranes Biochim Biophys Acta Biomembr 2014 1838 2492 2502 10.1016/j.bbamem.2014.05.022 PMC4125507 24878450 · DOI
  38. [38]Hu D Deng Y Jia F Jin Q Ji J Surface charge switchable supramolecular nanocarriers for nitric oxide synergistic photodynamic eradication of biofilms ACS Nano 2020 14 347 359 10.1021/acsnano.9b05493 31887012 · DOI
  39. [39]Liu H Yu Y Xue T Gan C Xie Y Wang D Li P Qian Z Ye T A nonenzymatic electrochemical sensor for the detection of hydrogen peroxide in vitro and in vivo fibrosis models Chin Chem Lett 2024 35 108574 10.1016/j.cclet.2023.108574 · DOI
  40. [40]Xiu W Shan J Yang K Xiao H Yuwen L Wang L Recent development of nanomedicine for the treatment of bacterial biofilm infections VIEW 2021 2 20200065 10.1002/VIW.20200065 · DOI
  41. [41]Gollmer A Arnbjerg J Blaikie FH Pedersen BW Breitenbach T Daasbjerg K Glasius M Ogilby PR Singlet Oxygen Sensor Green®: photochemical behavior in solution and in a mammalian cell Photochem Photobiol 2011 87 671 679 10.1111/j.1751-1097.2011.00900.x 21272007 · DOI
  42. [42]Huysseune A Larsen UG Larionova D Matthiesen CL Petersen SV Muller M Witten PE Bone formation in zebrafish: the significance of DAF-FM DA staining for nitric oxide detection Biomolecules 2023 13 1780 10.3390/biom13121780 38136650 PMC10742054 · DOI
  43. [43]Eruslanov E Kusmartsev S Identification of ROS using oxidized DCFDA and flow-cytometry Methods Mol Biol 2010 594 57 72 10.1007/978-1-60761-411-1_4 20072909 · DOI
  44. [44]Hsu Y-J Nain A Lin Y-F Tseng Y-T Li Y-J Sangili A Srivastava P Yu H-L Huang Y-F Huang C-C Self-redox reaction driven in situ formation of Cu2O/Ti3C2Tx nanosheets boost the photocatalytic eradication of multi-drug resistant bacteria from infected wound J Nanobiotechnol 2022 20 235 10.1186/s12951-022-01428-3 PMC9117998 35590324 · DOI
  45. [45]Votyakova TV Reynolds IJ Detection of hydrogen peroxide with Amplex Red: interference by NADH and reduced glutathione auto-oxidation Arch Biochem Biophys 2004 431 138 144 10.1016/j.abb.2004.07.025 15464736 · DOI
  46. [46]Skulachev V Bioenergetic aspects of apoptosis, necrosis and mitoptosis Apoptosis 2006 11 473 485 10.1007/s10495-006-5881-9 16532373 · DOI
  47. [47]Veisi H Sodium hypochlorite (NaOCl) Synlett 2007 2007 2607 2608 10.1055/s-2007-986658 · DOI
  48. [48]Puchtler H Meloan SN TERRY MS: On the history and mechanism of alizarin and alizarin red S stains for calcium J Histochem Cytochem 1969 17 110 124 10.1177/17.2.110 4179464 · DOI
  49. [49]Xiao G Cui Y Ducy P Karsenty G Franceschi RT Ascorbic acid-dependent activation of the osteocalcin promoter in MC3T3-E1 preosteoblasts: requirement for collagen matrix synthesis and the presence of an intact OSE2 sequence Mol Endocrinol 1997 11 1103 1113 10.1210/mend.11.8.9955 9212058 · DOI
  50. [50]Kawane T Qin X Jiang Q Miyazaki T Komori H Yoshida CA Matsuura-Kawata VKdS Sakane C Matsuo Y Nagai K Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation by regulating Fgfr2 and Fgfr3 Sci Rep 2018 8 13551 10.1038/s41598-018-31853-0 30202094 PMC6131145 · DOI
  51. [51]Seweryn A Alicka M Fal A Kornicka-Garbowska K Lawniczak-Jablonska K Ozga M Kuzmiuk P Godlewski M Marycz K Hafnium (IV) oxide obtained by atomic layer deposition (ALD) technology promotes early osteogenesis via activation of Runx2-OPN-mir21A axis while inhibits osteoclasts activity J Nanobiotechnol 2020 18 1 16 10.1186/s12951-020-00692-5 PMC7493872 32933533 · DOI
  52. [52]Wittmann C Chockley P Singh SK Pase L Lieschke GJ Grabher C Hydrogen peroxide in inflammation: messenger, guide, and assassin Adv Hematol 2012 2012 541471 10.1155/2012/541471 22737171 PMC3378963 · DOI · Paper page
  53. [53]Luo X Wan Q Cheng L Xu R Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis Front Cell Infect Microbiol 2022 12 908859 10.3389/fcimb.2022.908859 35937695 PMC9353524 · DOI
  54. [54]Cai C Chen X Li Y Jiang Q Advances in the role of sodium hypochlorite irrigant in chemical preparation of root canal treatment Biomed Res Int 2023 2023 8858283 10.1155/2023/8858283 36685672 PMC9859704 · DOI
  55. [55]Azim AA Aksel H Margaret Jefferson M Huang GT Comparison of sodium hypochlorite extrusion by five irrigation systems using an artificial root socket model and a quantitative chemical method Clin Oral Investig 2018 22 1055 1061 10.1007/s00784-017-2187-y 28748298 · DOI
  56. [56]Mei Z Gao D Hu D Zhou H Ma T Huang L Liu X Zheng R Zheng H Zhao P Activatable NIR-II photoacoustic imaging and photochemical synergistic therapy of MRSA infections using miniature Au/Ag nanorods Biomaterials 2020 251 120092 10.1016/j.biomaterials.2020.120092 32388165 · DOI
  57. [57]Badran Z Rahman B De Bonfils P Nun P Coeffard V Verron E Antibacterial nanophotosensitizers in photodynamic therapy: an update Drug Discov Today 2023 28 103493 10.1016/j.drudis.2023.103493 36657636 · DOI
  58. [58]Swimberghe RCD Coenye T De Moor RJG Meire MA Biofilm model systems for root canal disinfection: a literature review Int Endod J 2019 52 604 628 10.1111/iej.13050 30488449 · DOI

Authors
Zeng, Y., Hu, X., Cai, Z., Qiu, D., Ran, Y., Ding, Y., Shi, J., Cai, X., & Pan, Y.
Affiliations
Wenzhou Medical University (CN)
Corresponding author
  • Cai, Xiaojun
  • Pan, Yihuai
ORCID
Venue
Journal of Nanobiotechnology
Publisher
Springer Science and Business Media LLC
Published
2024-04-30
Volume
22
Issue
1
Pages
213-213
ISSN
1477-3155 (ISSN-L)
DOI
10.1186/s12951-024-02483-8
PMC
PMC11059741
OpenAlex
W4396518564
Cited by
48
References
57
Citations by year
2026: 16 · 2025: 28 · 2024: 4
FWCI
20.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Nanobiotechnology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Medicine and Health Science and Technology Plan Projects in Zhejiang province (2022RC212)
  • Wenzhou Major Science and Technology Special Project (ZY2022019)
  • Zhejiang Provincial Natural Science Foundation of China (LGF21H140005)
Topics
  • Health Sciences › Dentistry › Oral Surgery › Endodontics and Root Canal Treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Keywords
antimicrobial photodynamic therapy, nitric oxide, root canal irrigation, apical periodontitis, chlorin e6, biofilm eradication, alveolar bone healing, biosafety
MeSH terms
Animals, Anti-Infective Agents, Anti-Bacterial Agents, Bacterial Infections, Chlorophyllides, Male, Nitric Oxide, Periapical Periodontitis, Photochemotherapy, Root Canal Irrigants, Rats, Sprague-Dawley, Photosensitizing Agents, Biofilms, Rats, Nanoparticles

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review