Nanoparticle (Star Polymer) Delivery of Nitric Oxide Effectively Negates Pseudomonas aeruginosa Biofilm Formation
Abstract
Biofilms are increasingly recognized as playing a major role in human infectious diseases, as they can form on both living tissues and abiotic surfaces, with serious implications for applications that rely on prolonged exposure to the body such as implantable biomedical devices or catheters. Therefore, there is an urgent need to develop improved therapeutics to effectively eradicate unwanted biofilms. Recently, the biological signaling molecule nitric oxide (NO) was identified as a key regulator of dispersal events in biofilms. In this paper, we report a new class of core cross-linked star polymers designed to store and release nitric oxide, in a controlled way, for the dispersion of biofilms. First, core cross-linked star polymers were prepared by reversible addition-fragmentation chain transfer polymerization (RAFT) via an arm first approach. Poly(oligoethylene methoxy acrylate) chains were synthesized by RAFT polymerization, and then chain extended in the presence of 2-vinyl-4,4-dimethyl-5-oxazolone monomer (VDM) with N,N-methylenebis(acrylamide) employed as a cross-linker to yield functional core cross-linked star polymers. Spermine was successfully attached to the star core by reaction with VDM. Finally, the secondary amine groups were reacted with NO gas to yield NO-core cross-linked star polymers. The core cross-linked star polymers were found to release NO in a controlled, slow delivery in bacterial cultures showing great efficacy in preventing both cell attachment and biofilm formation in Pseudomonas aeruginosa over time via a nontoxic mechanism, confining bacterial growth to the suspended liquid.
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Nanoparticles able to decrease Pseudomonas aeruginosa biofilm formation by >70% compared with untreated controls.
“Furthermore, they found that nanoparticles were able to decrease Pseudomonas aeruginosa biofilm formation by > 70% compared with untreated controls 35 .”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [35]
Cites
Pal, S., Tak, Y. K., & Song, J. M. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.02218-06 · Cited by 4,042 · see citing works
Antibiotic resistance of bacterial biofilms
Høiby, N., Bjarnsholt, T., Givskov, M., Molin, S., & Ciofu, O. (2010) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2009.12.011 · Cited by 3,238 · see citing works
The world health report 2000 - Health systems: improving performance
Reinhardt, U., & Cheng, T.-M. (2000) · Europe PMC (PubMed Central) · doi:10.1590/s0042-96862000000800020 · Cited by 3,218 · see citing works
Understanding biofilm resistance to antibacterial agents
Davies, D. G. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1008 · Cited by 2,791 · see citing works
Targeting virulence: a new paradigm for antimicrobial therapy
Clatworthy, A. E., Pierson, E. R., & Hung, D. T. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.24 · Cited by 1,410 · see citing works
Should we stay or should we go: mechanisms and ecological consequences for biofilm dispersal
McDougald, D., Rice, S. A., Barraud, N., Steinberg, P. D., & Kjelleberg, S. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2695 · Cited by 881 · see citing works
Self-citationInvolvement of Nitric Oxide in Biofilm Dispersal of Pseudomonas aeruginosa
Barraud, N., Hassett, D. J., Hwang, S.-H., Rice, S. A., Kjelleberg, S. J., & Webb, J. S. (2006) · Journal of Bacteriology · doi:10.1128/jb.00779-06 · Cited by 786 · see citing works
Self-citationMeasurement of Nitric Oxide Production in Biological Systems by Using Griess Reaction Assay
Sun, J., Zhang, X., Broderick, M. P., & Fein, H. (2003) · Sensors · doi:10.3390/s30800276 · Cited by 780 · see citing works
Maragos, C. M., Morley, D., Wink, D. A., Dunams, T. M., Saavedra, J. E., Hoffman, A., Bove, A. A., Isaac, L., Hrabie, J. A., & Keefer, L. K. (1991) · Journal of Medicinal Chemistry · doi:10.1021/jm00115a013 · Cited by 722 · see citing works
End group removal and modification of RAFT polymers
Willcock, H., & O’Reilly, R. K. (2009) · Polymer Chemistry · doi:10.1039/b9py00340a · Cited by 606 · see citing works
Mechanism of Nitric Oxide Release from S-Nitrosothiols
Singh, R. J., Hogg, N., Joseph, J., & Kalyanaraman, B. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.31.18596 · Cited by 600 · see citing works
Barraud, N., Schleheck, D., Klebensberger, J., Webb, J. S., Hassett, D. J., Rice, S. A., & Kjelleberg, S. J. (2009) · Journal of Bacteriology · doi:10.1128/jb.00975-09 · Cited by 515 · see citing works
Self-citationNitric oxide, a double edged sword in cancer biology: Searching for therapeutic opportunities
D, S. M. M., Bronte, V., & Nitti, D. (2006) · Medicinal Research Reviews · doi:10.1002/med.20092 · Cited by 480 · see citing works
The use of nanoparticles in anti-microbial materials and their characterization
Weir, E., Lawlor, A., Whelan, Á. M., & Regan, F. B. (2008) · The Analyst · doi:10.1039/b715532h · Cited by 302 · see citing works
Barraud, N., Storey, M. V., Moore, Z. P., Webb, J. S., Rice, S. A., & Kjelleberg, S. (2009) · Microbial Biotechnology · doi:10.1111/j.1751-7915.2009.00098.x · Cited by 289 · see citing works
Self-citationNitric Oxide-Releasing Polymers Containing the [N(O)NO]<sup>-</sup>Group
Smith, D. J., Chakravarthy, D., Pulfer, S., Simmons, M. L., Hrabie, J. A., Citro, M. L., Saavedra, J. E., Davies, K. M., Hutsell, T. C., Mooradian, D. L., et al. (1996) · Journal of Medicinal Chemistry · doi:10.1021/jm950652b · Cited by 208 · see citing works
Davies, K. M., Wink, D. A., Saavedra, J. E., & Keefer, L. K. (2001) · Journal of the American Chemical Society · doi:10.1021/ja002899q · Cited by 208 · see citing works
The Phosphodiesterase DipA (PA5017) Is Essential for Pseudomonas aeruginosa Biofilm Dispersion
Roy, A. B., Petrova, O. E., & Sauer, K. (2012) · Journal of Bacteriology · doi:10.1128/jb.05346-11 · Cited by 206 · see citing works
Yamamoto, T., & Bing, R. J. (2000) · Proceedings of The Society for Experimental Biology and Medicine · doi:10.1046/j.1525-1373.2000.22525.x · Cited by 193 · see citing works
A platform for nitric oxide delivery
Kim, J., Saravanakumar, G., Choi, H. W., Park, D., & Kim, W. J. (2013) · Journal of Materials Chemistry B · doi:10.1039/c3tb21259a · Cited by 167 · see citing works
Cephalosporin‐3′‐diazeniumdiolates: Targeted NO‐Donor Prodrugs for Dispersing Bacterial Biofilms
Barraud, N., Kardak, B. G., Yepuri, N. R., Howlin, R. P., Webb, J. S., Faust, S. N., Kjelleberg, S. J., Rice, S. A., & Kelso, M. J. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201202414 · Cited by 159 · see citing works
Self-citationBonavida, B., Baritaki, S., Huerta‐Yépez, S., Vega, M. I., Chatterjee, D., & Yeung, K. C. (2008) · Nitric Oxide · doi:10.1016/j.niox.2008.04.018 · Cited by 152 · see citing works
Macromolecular Ligands for Gadolinium MRI Contrast Agents
Li, Y., Beija, M., Laurent, S., Elst, L. V., Müller, R. N., Duong, H. T. T., Lowe, A. B., Davis, T. P., & Boyer, C. A. (2012) · Macromolecules · doi:10.1021/ma300521c · Cited by 151 · see citing works
Self-citationNitric Oxide Regulation of Cyclic di-GMP Synthesis and Hydrolysis in Shewanella woodyi
Liu, N., Xu, Y., Hossain, S., Huang, N., Coursolle, D., Gralnick, J. A., & Boon, E. M. (2012) · Biochemistry · doi:10.1021/bi201753f · Cited by 150 · see citing works
Synthesis of Functional Core, Star Polymers via RAFT Polymerization for Drug Delivery Applications
Liu, J., Duong, H. T. T., Whittaker, M. R., et al. (2012) · Macromolecular Rapid Communications · doi:10.1002/marc.201200029 · Cited by 150 · see citing works
Self-citationIntracellular nitric oxide delivery from stable NO-polymeric nanoparticle carriers
Duong, H. T. T., Kamarudin, Z. M., Erlich, R. B., Li, Y., Jones, M. W., Kavallaris, M., Boyer, C. A., & Davis, T. P. (2012) · Chemical Communications · doi:10.1039/c2cc37181b · Cited by 137 · see citing works
Self-citationInfluence of Scaffold Size on Bactericidal Activity of Nitric Oxide-Releasing Silica Nanoparticles
Carpenter, A. W., Slomberg, D. L., Rao, K. S., & Schoenfisch, M. H. (2011) · ACS Nano · doi:10.1021/nn202054f · Cited by 134 · see citing works
Water-Soluble Nitric Oxide-Releasing Gold Nanoparticles
Polizzi, M. A., Stasko, N. A., & Schoenfisch, M. H. (2007) · Langmuir · doi:10.1021/la0633841 · Cited by 133 · see citing works
Ferreira, J., Syrett, J. A., Whittaker, M. R., et al. (2011) · Polymer Chemistry · doi:10.1039/c1py00102g · Cited by 117 · see citing works
Functional, star polymeric molecular carriers, built from biodegradable microgel/nanogel cores
Syrett, J. A., Haddleton, D. M., Whittaker, M. R., Davis, T. P., & Boyer, C. A. (2010) · Chemical Communications · doi:10.1039/c0cc04532b · Cited by 114 · see citing works
Self-citationBratasz, A., Weir, N. M., Parinandi, N. L., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511250103 · Cited by 96 · see citing works
Synthesis and Characterization of Polymethacrylate-Based Nitric Oxide Donors
Parzuchowski, P. G., Frost, M. C., & Meyerhoff, M. E. (2002) · Journal of the American Chemical Society · doi:10.1021/ja020268l · Cited by 93 · see citing works
Micelles for Delivery of Nitric Oxide
Jo, Y. S., van der Vlies, A. J., Gantz, J., Thacher, T. N., Antonijevic, S., Cavadini, S., Demurtas, D., Stergiopulos, N., & Hubbell, J. A. (2009) · Journal of the American Chemical Society · doi:10.1021/ja905123t · Cited by 86 · see citing works
Kim, J., Lee, Y., Singha, K., Kim, H. W., Shin, J. H., Jo, S., Han, D. K., & Kim, W. J. (2011) · Bioconjugate Chemistry · doi:10.1021/bc100405c · Cited by 85 · see citing works
HNO and NO Release from a Primary Amine-Based Diazeniumdiolate As a Function of pH
Salmon, D. J., de Holding, C. L. T., Thomas, L., Peterson, K. V., Goodman, G. P., Saavedra, J. E., Srinivasan, A., Davies, K. M., Keefer, L. K., & Miranda, K. M. (2011) · Inorganic Chemistry · doi:10.1021/ic101736e · Cited by 80 · see citing works
Barnes, R. J., Bandi, R. R., Wong, W. S., Barraud, N., McDougald, D., Fane, A. G., Kjelleberg, S. J., & Rice, S. A. (2013) · Biofouling · doi:10.1080/08927014.2012.760069 · Cited by 76 · see citing works
Self-citationLevere, M. E., Ho, H. T., Pascual, S., & Fontaine, L. (2011) · Polymer Chemistry · doi:10.1039/c1py00320h · Cited by 64 · see citing works
Ho, H. T., Levere, M. E., Fournier, D., Montembault, V., Pascual, S., & Fontaine, L. (2012) · Australian Journal of Chemistry · doi:10.1071/ch12192 · Cited by 60 · see citing works
Flemming, H.-C., Szewzyk, U., & Wingender, J. (2011) · Springer series on biofilms · doi:10.1007/978-3-642-19940-0 · Cited by 59 · see citing works
Yepuri, N. R., Barraud, N., Mohammadi, N. S., Kardak, B. G., Kjelleberg, S. J., Rice, S. A., & Kelso, M. J. (2013) · Chemical Communications · doi:10.1039/c3cc40869h · Cited by 53 · see citing works
Self-citationDuan, S., Cai, S., Yang, Q., & Forrest, M. L. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.01.026 · Cited by 42 · see citing works
Momin, E. N., Schwab, K. E., Chaichana, K. L., Miller‐Lotan, R., Levy, A. P., & Tamargo, R. J. (2009) · Neurosurgery · doi:10.1227/01.neu.0000356974.14230.b8 · Cited by 32 · see citing works
Synthesis and postfunctionalization of well‐defined star polymers via “double” click chemistry
Boyer, C. A., Whittaker, M. R., & Davis, T. P. (2011) · Journal of Polymer Science Part A Polymer Chemistry · doi:10.1002/pola.25001 · Cited by 30 · see citing works
Self-citationBasuki, J. S., Duong, H. T. T., Macmillan, A., Whan, R. M., Boyer, C. A., & Davis, T. P. (2013) · Macromolecules · doi:10.1021/ma401171d · Cited by 21 · see citing works
Self-citationLocalization of HydrophobicN-Diazeniumdiolates in Aqueous Micellar Solution
Mohr, P. C., Mohr, A., Vila, T. P., & Korth, H. (2010) · Langmuir · doi:10.1021/la101619y · Cited by 9 · see citing works
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Nanotechnology approaches for global infectious diseases
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Nitric oxide–releasing macromolecular scaffolds for antibacterial applications
Yang, L., Feura, E. S., Ahonen, M. J. R., & Schoenfisch, M. H. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201800155 · Cited by 218 · see citing works
Nitric oxide regulation of bacterial biofilms
Arora, D. P., Hossain, S., Xu, Y., & Boon, E. M. (2015) · Biochemistry · doi:10.1021/bi501476n · Cited by 206 · see citing works
Ahmadi, M. S., Lee, H. H., Sanchez, D. A., Friedman, A. J., Tar, M. T., Davies, K. P., Nosanchuk, J. D., & Martinez, L. R. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02659-15 · Cited by 41 · see citing works
- Authors
- Duong, H. T. T., Jung, K., Kutty, S. K., Agustina, S., Adnan, N. N. M., Basuki, J. S., Kumar, N., Davis, T. P., Barraud, N., & Boyer, C.
- Affiliations
- UNSW Sydney (AU)
- University of Warwick (GB)
- Corresponding author
- Davis, Thomas P.
- Barraud, Nicolas
- Boyer, Cyrille
- ORCID
- Venue
- Biomacromolecules
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-06-10
- Volume
- 15
- Issue
- 7
- Pages
- 2583-2589
- ISSN
- 1525-7797 (ISSN-L)
- 1526-4602
- OpenAlex
- W2057460683
- Cited by
- 126
- References
- 45
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 9 · 2022: 3 · 2021: 22 · 2020: 11 · 2019: 9 · 2018: 17 · 2017: 10 · 2016: 16 · 2015: 14 · 2014: 2
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomacromolecules (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Australian Research Council (DE120101604, FT 120100096)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Physical Sciences › Chemistry › Organic Chemistry › Advanced Polymer Synthesis and Characterization
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- nitric oxide delivery, star polymers, Pseudomonas aeruginosa, biofilm formation, biofilm dispersal, RAFT polymerization, N,N'-methylenebisacrylamide, spermine, controlled release
- MeSH terms
- Anti-Bacterial Agents, Drug Carriers, Kinetics, Methacrylates, Microbial Sensitivity Tests, Nitric Oxide, Polyethylenes, Pseudomonas aeruginosa, Spectroscopy, Fourier Transform Infrared, Biofilms, Nanoparticles, Polymerization
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