Dual antibacterial drug-loaded nanoparticles synergistically improve treatment of Streptococcus mutans biofilms
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.actbio.2020.08.032 http://hdl.handle.net/11449/209544 |
Resumo: | Dental caries (i.e., tooth decay), which is caused by biofilm formation on tooth surfaces, is the most prevalent oral disease worldwide. Unfortunately, many anti-biofilm drugs lack efficacy within the oral cavity due to poor solubility, retention, and penetration into biofilms. While drug delivery systems (DDS) have been developed to overcome these hurdles and improve traditional antimicrobial treatments, including farnesol, efficacy is still modest due to myriad resistance mechanisms employed by biofilms, suggesting that synergistic drug treatments may be more efficacious. Streptococcus mutans (S. mutans), a cariogenic pathogen and biofilm forming model organism, has several key virulence factors including acidogenicity and exopolysaccharide (EPS) matrix synthesis. Flavonoids, such as myricetin, can reduce both biofilm acidogenicity and EPS synthesis. Therefore, a nanoparticle carrier (NPC) DDS with flexibility to co-load farnesol in the hydrophobic core and myricetin within the cationic corona, was tested in vitro using established and developing S. mutans biofilms. Co-loaded NPC treatments effectively disrupted biofilm biomass (Le., dry weight) and reduced biofilm viability by similar to 3 log CFU/mL versus single drug-only controls in developing biofilms, suggesting dual-drug delivery exhibits synergistic anti-biofilm effects. Mechanistic studies revealed that co-loaded NPCs synergistically inhibited planktonic bacterial growth compared to controls and reduced S. mutans acidogenicity due to decreased atpD expression, a gene associated with acid tolerance. Moreover, the myricetin-loaded NPC corona enhanced NPC binding to tooth-mimetic surfaces, which can increase drug efficacy through improved retention at the biofilm-apatite interface. Altogether, these findings suggest promise for co-delivery of myricetin and farnesol DDS as an alternative anti-biofilm treatment to prevent dental caries. Published by Elsevier Ltd on behalf of Acta Materialia Inc. |
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Dual antibacterial drug-loaded nanoparticles synergistically improve treatment of Streptococcus mutans biofilmsBiofilmNanoparticleCo-loadingMyricetinFarnesolDrug deliverySynergyDental caries (i.e., tooth decay), which is caused by biofilm formation on tooth surfaces, is the most prevalent oral disease worldwide. Unfortunately, many anti-biofilm drugs lack efficacy within the oral cavity due to poor solubility, retention, and penetration into biofilms. While drug delivery systems (DDS) have been developed to overcome these hurdles and improve traditional antimicrobial treatments, including farnesol, efficacy is still modest due to myriad resistance mechanisms employed by biofilms, suggesting that synergistic drug treatments may be more efficacious. Streptococcus mutans (S. mutans), a cariogenic pathogen and biofilm forming model organism, has several key virulence factors including acidogenicity and exopolysaccharide (EPS) matrix synthesis. Flavonoids, such as myricetin, can reduce both biofilm acidogenicity and EPS synthesis. Therefore, a nanoparticle carrier (NPC) DDS with flexibility to co-load farnesol in the hydrophobic core and myricetin within the cationic corona, was tested in vitro using established and developing S. mutans biofilms. Co-loaded NPC treatments effectively disrupted biofilm biomass (Le., dry weight) and reduced biofilm viability by similar to 3 log CFU/mL versus single drug-only controls in developing biofilms, suggesting dual-drug delivery exhibits synergistic anti-biofilm effects. Mechanistic studies revealed that co-loaded NPCs synergistically inhibited planktonic bacterial growth compared to controls and reduced S. mutans acidogenicity due to decreased atpD expression, a gene associated with acid tolerance. Moreover, the myricetin-loaded NPC corona enhanced NPC binding to tooth-mimetic surfaces, which can increase drug efficacy through improved retention at the biofilm-apatite interface. Altogether, these findings suggest promise for co-delivery of myricetin and farnesol DDS as an alternative anti-biofilm treatment to prevent dental caries. Published by Elsevier Ltd on behalf of Acta Materialia Inc.National Institutes of HealthNational Science FoundationFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Institute of Dental & Craniofacial Research of the National Institutes of HealthUniv Rochester, Sch Med & Dent, Translat Biomed Sci, Rochester, NY USAUniv Rochester, Dept Biomed Engn, Rochester, NY USAUniv Rochester, Dept Chem, Rochester, NY USAUniv Penn, Dept Orthodont, Ctr Innovat & Precis Dent, Sch Dent Med, Philadelphia, PA USASao Paulo State Univ, Dept Dent Mat & Prosthodont, Araraquara, SP, BrazilUniv Rochester, Mat Sci Program, Rochester, NY USAUniv Rochester, Dept Orthopaed, Rochester, NY USAUniv Rochester, Ctr Musculoskeletal Res, Rochester, NY USAUniv Rochester, Ctr Oral Biol, Rochester, NY USAUniv Rochester, Dept Chem Engn, Rochester, NY 14627 USASao Paulo State Univ, Dept Dent Mat & Prosthodont, Araraquara, SP, BrazilNational Institutes of Health: R01 DE018023National Institutes of Health: F31 DE026944National Science Foundation: DMR 1206219FAPESP: FAPESP 2019/01429-4Elsevier B.V.Univ RochesterUniv PennUniversidade Estadual Paulista (Unesp)Sims, Kenneth R.Maceren, Julian P.Liu, YuanRocha, Guilherme R. [UNESP]Koo, HyunBenoit, Danielle S. W.2021-06-25T12:21:42Z2021-06-25T12:21:42Z2020-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article418-431http://dx.doi.org/10.1016/j.actbio.2020.08.032Acta Biomaterialia. Oxford: Elsevier Sci Ltd, v. 115, p. 418-431, 2020.1742-7061http://hdl.handle.net/11449/20954410.1016/j.actbio.2020.08.032WOS:000577511200032Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengActa Biomaterialiainfo:eu-repo/semantics/openAccess2021-10-23T19:28:14Zoai:repositorio.unesp.br:11449/209544Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T20:00:43.687489Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Dual antibacterial drug-loaded nanoparticles synergistically improve treatment of Streptococcus mutans biofilms |
title |
Dual antibacterial drug-loaded nanoparticles synergistically improve treatment of Streptococcus mutans biofilms |
spellingShingle |
Dual antibacterial drug-loaded nanoparticles synergistically improve treatment of Streptococcus mutans biofilms Sims, Kenneth R. Biofilm Nanoparticle Co-loading Myricetin Farnesol Drug delivery Synergy |
title_short |
Dual antibacterial drug-loaded nanoparticles synergistically improve treatment of Streptococcus mutans biofilms |
title_full |
Dual antibacterial drug-loaded nanoparticles synergistically improve treatment of Streptococcus mutans biofilms |
title_fullStr |
Dual antibacterial drug-loaded nanoparticles synergistically improve treatment of Streptococcus mutans biofilms |
title_full_unstemmed |
Dual antibacterial drug-loaded nanoparticles synergistically improve treatment of Streptococcus mutans biofilms |
title_sort |
Dual antibacterial drug-loaded nanoparticles synergistically improve treatment of Streptococcus mutans biofilms |
author |
Sims, Kenneth R. |
author_facet |
Sims, Kenneth R. Maceren, Julian P. Liu, Yuan Rocha, Guilherme R. [UNESP] Koo, Hyun Benoit, Danielle S. W. |
author_role |
author |
author2 |
Maceren, Julian P. Liu, Yuan Rocha, Guilherme R. [UNESP] Koo, Hyun Benoit, Danielle S. W. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Univ Rochester Univ Penn Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Sims, Kenneth R. Maceren, Julian P. Liu, Yuan Rocha, Guilherme R. [UNESP] Koo, Hyun Benoit, Danielle S. W. |
dc.subject.por.fl_str_mv |
Biofilm Nanoparticle Co-loading Myricetin Farnesol Drug delivery Synergy |
topic |
Biofilm Nanoparticle Co-loading Myricetin Farnesol Drug delivery Synergy |
description |
Dental caries (i.e., tooth decay), which is caused by biofilm formation on tooth surfaces, is the most prevalent oral disease worldwide. Unfortunately, many anti-biofilm drugs lack efficacy within the oral cavity due to poor solubility, retention, and penetration into biofilms. While drug delivery systems (DDS) have been developed to overcome these hurdles and improve traditional antimicrobial treatments, including farnesol, efficacy is still modest due to myriad resistance mechanisms employed by biofilms, suggesting that synergistic drug treatments may be more efficacious. Streptococcus mutans (S. mutans), a cariogenic pathogen and biofilm forming model organism, has several key virulence factors including acidogenicity and exopolysaccharide (EPS) matrix synthesis. Flavonoids, such as myricetin, can reduce both biofilm acidogenicity and EPS synthesis. Therefore, a nanoparticle carrier (NPC) DDS with flexibility to co-load farnesol in the hydrophobic core and myricetin within the cationic corona, was tested in vitro using established and developing S. mutans biofilms. Co-loaded NPC treatments effectively disrupted biofilm biomass (Le., dry weight) and reduced biofilm viability by similar to 3 log CFU/mL versus single drug-only controls in developing biofilms, suggesting dual-drug delivery exhibits synergistic anti-biofilm effects. Mechanistic studies revealed that co-loaded NPCs synergistically inhibited planktonic bacterial growth compared to controls and reduced S. mutans acidogenicity due to decreased atpD expression, a gene associated with acid tolerance. Moreover, the myricetin-loaded NPC corona enhanced NPC binding to tooth-mimetic surfaces, which can increase drug efficacy through improved retention at the biofilm-apatite interface. Altogether, these findings suggest promise for co-delivery of myricetin and farnesol DDS as an alternative anti-biofilm treatment to prevent dental caries. Published by Elsevier Ltd on behalf of Acta Materialia Inc. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-10-01 2021-06-25T12:21:42Z 2021-06-25T12:21:42Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.actbio.2020.08.032 Acta Biomaterialia. Oxford: Elsevier Sci Ltd, v. 115, p. 418-431, 2020. 1742-7061 http://hdl.handle.net/11449/209544 10.1016/j.actbio.2020.08.032 WOS:000577511200032 |
url |
http://dx.doi.org/10.1016/j.actbio.2020.08.032 http://hdl.handle.net/11449/209544 |
identifier_str_mv |
Acta Biomaterialia. Oxford: Elsevier Sci Ltd, v. 115, p. 418-431, 2020. 1742-7061 10.1016/j.actbio.2020.08.032 WOS:000577511200032 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Acta Biomaterialia |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
418-431 |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129149561208832 |