{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:42:55Z","timestamp":1791380575581,"version":"4.3.3"},"reference-count":36,"publisher":"IOP Publishing","issue":"47","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"name":"Waterloo Institute for Nanotechnology"},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["RGPIN-2021-03072"],"award-info":[{"award-number":["RGPIN-2021-03072"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Nanotechnology"],"published-print":{"date-parts":[[2024,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bacterial vaginosis (BV) is a common vaginal infection affecting millions of women. Vaginal anaerobic dysbiosis occurs when <jats:italic>Lactobacillus<\/jats:italic> spp., the dominant flora in healthy vagina is replaced by certain overgrown anaerobes, resulting in unpleasant symptoms such as vaginal discharge and odor. With a high recurrence rate, BV also severely impacts the overall quality of life of childbearing women by inducing preterm delivery and increasing the risks of pelvic inflammatory disease and sexually transmitted infections. Among various BV-associated bacteria, <jats:italic>Gardnerella vaginalis<\/jats:italic> (<jats:italic>G. vaginalis<\/jats:italic>) has been identified as a primary pathogen since it has been isolated from almost all women carrying BV and exhibits higher virulence potential over other bacteria. When dealing with BV relapse, intravaginal drug delivery systems are superior to conventional oral antibiotic therapies in improving therapeutic efficacy owing to more effective drug dose, reduced drug resistance and minimized side effects such as stomach irritation. Traditional intravaginal drug administration generally involves solids, semi-solids and delivery devices inserted into the vaginal lumen to achieve sustained drug release. However, they are mostly designed for continuous drug release and are not preventative therapies, resulting in severe side effects caused by excess dosing. Stimuli-responsive systems that can release drug only when needed (\u2018on-demand\u2019) can help diminish these negative side effects. Hence, we developed a bacteria-responsive liposomal platform for the prevention and treatment of BV. This platform demonstrated sustained drug release in the presence of vaginolysin, a toxin secreted specifically by <jats:italic>G. vaginalis<\/jats:italic>. We prepared four liposome formulations and evaluated their responsiveness to <jats:italic>G. vaginalis<\/jats:italic>. The results demonstrated that the liposome formulations could achieve cumulative drug release ranging from 46.7% to 51.8% over a 3\u20135 d period in response to <jats:italic>G. vaginalis<\/jats:italic> and hardly any drug release in the presence of <jats:italic>Lactobacillus crispatus<\/jats:italic> (<jats:italic>L. crispatus<\/jats:italic>), indicating the high specificity of the system. Overall, the bacteria-responsive drug release platform has great potential, since it will be the first time to realize sustained drug release stimulated by a specific pathogen for BV prevention and treatment. This on-demand therapy can potentially provide relief to the millions of women affected by BV.<\/jats:p>","DOI":"10.1088\/1361-6528\/ad7143","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T20:06:10Z","timestamp":1724357170000},"page":"475101","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Bacteria-responsive drug release platform for the local treatment of bacterial vaginosis"],"prefix":"10.1088","volume":"35","author":[{"given":"Chuying","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4729-9970","authenticated-orcid":true,"given":"Emmanuel A","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"nanoad7143bib1","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1097\/OLQ.0000000000000972","article-title":"High global burden and costs of bacterial vaginosis: a systematic review and meta-analysis","volume":"46","author":"Peebles","year":"2019","journal-title":"Sex. Transm. Dis."},{"key":"nanoad7143bib2","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.addr.2015.06.008","article-title":"New strategies for local treatment of vaginal infections","volume":"92","author":"Palmeira-de-Oliveira","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"nanoad7143bib3","doi-asserted-by":"publisher","first-page":"iv16","DOI":"10.1136\/sti.2006.023119","article-title":"Bacterial vaginosis","volume":"82","author":"Keane","year":"2006","journal-title":"Sex. Transm. Infect."},{"key":"nanoad7143bib4","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.1093\/infdis\/jiw159","article-title":"Current treatment of bacterial vaginosis-limitations and need for innovation","volume":"214","author":"Bradshaw","year":"2016","journal-title":"J. Infect. Dis."},{"key":"nanoad7143bib5","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1089\/jwh.2018.7383","article-title":"Characterization and treatment of recurrent bacterial vaginosis","volume":"28","author":"Faught","year":"2019","journal-title":"J. Womens Health"},{"key":"nanoad7143bib6","doi-asserted-by":"publisher","first-page":"217","DOI":"10.3390\/pharmaceutics11050217","article-title":"Modifications in vaginal microbiota and their influence on drug release: challenges and opportunities","volume":"11","author":"Leyva-G\u00f3mez","year":"2019","journal-title":"Pharmaceutics"},{"key":"nanoad7143bib7","doi-asserted-by":"publisher","first-page":"168","DOI":"10.3389\/fcimb.2020.00168","article-title":"Gardnerella vaginalis as a cause of bacterial vaginosis: appraisal of the evidence from in vivo models","volume":"10","author":"Morrill","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"nanoad7143bib8","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1093\/infdis\/jiv338","article-title":"Influence of biofilm formation by gardnerella vaginalis and other anaerobes on bacterial vaginosis","volume":"212","author":"Machado","year":"2015","journal-title":"J. Infect. Dis."},{"key":"nanoad7143bib9","doi-asserted-by":"publisher","first-page":"4544","DOI":"10.1128\/IAI.00627-13","article-title":"Vaginolysin drives epithelial ultrastructural responses to gardnerella vaginalis","volume":"81","author":"Randis","year":"2013","journal-title":"Infect. Immun."},{"key":"nanoad7143bib10","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.resmic.2017.02.011","article-title":"Gardnerella vaginalis diversity and ecology in relation to vaginal symptoms","volume":"168","author":"Schellenberg","year":"2017","journal-title":"Res. Microbiol."},{"key":"nanoad7143bib11","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3390\/toxins7010110","article-title":"The cytolytic activity of vaginolysin strictly depends on cholesterol and is potentiated by human CD59","volume":"7","author":"Zilnyte","year":"2015","journal-title":"Toxins"},{"key":"nanoad7143bib12","doi-asserted-by":"publisher","first-page":"eabb9853","DOI":"10.1126\/sciadv.abb9853","article-title":"Anti-\u03b14\u03b27 monoclonal antibody\u2013conjugated nanoparticles block integrin \u03b14\u03b27 on intravaginal T cells in rhesus macaques","volume":"6","author":"Yang","year":"2020","journal-title":"Sci. Adv."},{"key":"nanoad7143bib13","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1177\/0885328217739451","article-title":"Dynamic mechanical behaviour of nanoparticle loaded biodegradable PVA films for vaginal drug delivery","volume":"32","author":"Traore","year":"2018","journal-title":"J. Biomater. Appl."},{"key":"nanoad7143bib14","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jconrel.2018.03.010","article-title":"Implant delivering hydroxychloroquine attenuates vaginal T lymphocyte activation and inflammation","volume":"277","author":"Chen","year":"2018","journal-title":"J. Control. Release"},{"key":"nanoad7143bib15","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/j.jconrel.2023.12.043","article-title":"pH-sensitive dual-preventive siRNA-based nanomicrobicide reactivates autophagy and inhibits HIV infection in vaginal CD4+ cells","volume":"366","author":"Yang","year":"2024","journal-title":"J. Control. Release"},{"key":"nanoad7143bib16","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.ijpharm.2017.06.076","article-title":"Thermoplastic polyurethane-based intravaginal rings for prophylaxis and treatment of (recurrent) bacterial vaginosis","volume":"529","author":"Verstraete","year":"2017","journal-title":"Int. J. Pharm."},{"key":"nanoad7143bib17","doi-asserted-by":"publisher","first-page":"259","DOI":"10.3109\/13625187.2014.980501","article-title":"Women\u2019s experiences, preferences and perceptions regarding vaginal products: results from a cross-sectional web-based survey in portugal","volume":"20","author":"Palmeira-de-Oliveira","year":"2015","journal-title":"Eur. J. Contracept. Reprod. Health Care"},{"key":"nanoad7143bib18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119659","article-title":"Bacterial vaginosis: standard treatments and alternative strategies","volume":"587","author":"Tom\u00e1s","year":"2020","journal-title":"Int. J. Pharm."},{"key":"nanoad7143bib19","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2020.573211","article-title":"Modulation of efficient Diiodo-BODIPY in vitro phototoxicity to cancer cells by carbon nano-onions","volume":"8","author":"Bartelmess","year":"2020","journal-title":"Front. Chem."},{"key":"nanoad7143bib20","doi-asserted-by":"publisher","first-page":"50","DOI":"10.4103\/2230-973X.147233","article-title":"Formulation and evaluation of clindamycin HCL in situ gel for vaginal application","volume":"5","author":"Patel","year":"2015","journal-title":"Int. J. Pharm. Invest."},{"key":"nanoad7143bib21","doi-asserted-by":"publisher","first-page":"59","DOI":"10.2478\/v10007-012-0009-y","article-title":"Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulations for vaginal application","volume":"62","author":"E-s A","year":"2012","journal-title":"Acta Pharm. Zagreb. Croat."},{"key":"nanoad7143bib22","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1080\/03639045.2017.1328434","article-title":"A novel pH-responsive hydrogel-based on calcium alginate engineered by the previous formation of polyelectrolyte complexes (PECs) intended to vaginal administration","volume":"43","author":"Ferreira","year":"2017","journal-title":"Drug Dev. Ind. Pharm."},{"key":"nanoad7143bib23","doi-asserted-by":"publisher","first-page":"6265","DOI":"10.1039\/C6CC01269H","article-title":"A charge-adaptive nanosystem for prolonged and enhanced in vivo antibiotic delivery","volume":"52","author":"Chu","year":"2016","journal-title":"Chem. Commun."},{"key":"nanoad7143bib24","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1016\/j.colsurfb.2017.07.049","article-title":"pH-responsive chitosan nanoparticles from a novel twin-chain anionic amphiphile for controlled and targeted delivery of vancomycin","volume":"158","author":"Kalhapure","year":"2017","journal-title":"Colloids Surf. B"},{"key":"nanoad7143bib25","doi-asserted-by":"publisher","first-page":"11686","DOI":"10.1021\/acsnano.9b05608","article-title":"pH-switchable antimicrobial nanofiber networks of hydrogel eradicate biofilm and rescue stalled healing in chronic wounds","volume":"13","author":"Wang","year":"2019","journal-title":"ACS Nano"},{"key":"nanoad7143bib26","doi-asserted-by":"publisher","first-page":"4279","DOI":"10.1021\/nn3008383","article-title":"Surface charge-switching polymeric nanoparticles for bacterial cell wall-targeted delivery of antibiotics","volume":"6","author":"Radovic-Moreno","year":"2012","journal-title":"ACS Nano"},{"key":"nanoad7143bib27","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1039\/c7tb02682j","article-title":"pH-activated nanoparticles with targeting for the treatment of oral plaque biofilm","volume":"6","author":"Zhou","year":"2018","journal-title":"J. Mater. Chem. B"},{"key":"nanoad7143bib28","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202000511","article-title":"Ag nanoparticles cluster with pH\u2010triggered reassembly in targeting antimicrobial applications","volume":"30","author":"Anon","year":"2020","journal-title":"Adv. Funct. Mater."},{"key":"nanoad7143bib29","doi-asserted-by":"publisher","DOI":"10.1016\/j.matdes.2020.109021","article-title":"Reactive oxygen species-sensitive thioketal-linked mesoporous silica nanoparticles as drug carrier for effective antibacterial activity","volume":"195","author":"Li","year":"2020","journal-title":"Mater. Des."},{"key":"nanoad7143bib30","doi-asserted-by":"publisher","first-page":"2920","DOI":"10.1038\/s41467-018-05342-x","article-title":"Topical ferumoxytol nanoparticles disrupt biofilms and prevent tooth decay in vivo via intrinsic catalytic activity","volume":"9","author":"Liu","year":"2018","journal-title":"Nat. Commun."},{"key":"nanoad7143bib31","doi-asserted-by":"publisher","first-page":"6200","DOI":"10.1002\/smll.201601729","article-title":"Bacterial hyaluronidase self-triggered prodrug release for chemo-photothermal synergistic treatment of bacterial infection","volume":"12","author":"Ji","year":"2016","journal-title":"Small Weinh. Bergstr. Ger."},{"key":"nanoad7143bib32","doi-asserted-by":"publisher","first-page":"4355","DOI":"10.1021\/ja211279u","article-title":"Lipase-sensitive polymeric triple-layered nanogel for \u201con-demand\u201d drug delivery","volume":"134","author":"Xiong","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"nanoad7143bib33","doi-asserted-by":"publisher","first-page":"4063","DOI":"10.1021\/acsomega.8b03137","article-title":"Bacteria-responsive single and core\u2013shell nanofibrous membranes based on polycaprolactone\/poly(ethylene succinate) for on-demand release of biocides","volume":"4","author":"Abdali","year":"2019","journal-title":"ACS Omega"},{"key":"nanoad7143bib34","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsusc.2020.146806","article-title":"A pH and hyaluronidase dual-responsive multilayer-based drug delivery system for resisting bacterial infection","volume":"527","author":"Ayaz","year":"2020","journal-title":"Appl. Surf. Sci."},{"key":"nanoad7143bib35","doi-asserted-by":"publisher","first-page":"14299","DOI":"10.1021\/acsami.7b15678","article-title":"Bacteria-targeting nanoparticles with microenvironment-responsive antibiotic release to eliminate intracellular staphylococcus aureus and associated infection","volume":"10","author":"Yang","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"nanoad7143bib36","doi-asserted-by":"publisher","first-page":"71","DOI":"10.3109\/08982109409037030","article-title":"A polyol dilution method for mass production of liposomes","volume":"4","author":"Kikuchi","year":"1994","journal-title":"J. Liposome Res."}],"container-title":["Nanotechnology"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad7143","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad7143\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad7143","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad7143\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad7143\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad7143\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad7143\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad7143\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T07:21:54Z","timestamp":1725434514000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad7143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,4]]},"references-count":36,"journal-issue":{"issue":"47","published-online":{"date-parts":[[2024,9,4]]},"published-print":{"date-parts":[[2024,11,18]]}},"URL":"https:\/\/doi.org\/10.1088\/1361-6528\/ad7143","relation":{},"ISSN":["0957-4484","1361-6528"],"issn-type":[{"value":"0957-4484","type":"print"},{"value":"1361-6528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,4]]},"assertion":[{"value":"Bacteria-responsive drug release platform for the local treatment of bacterial vaginosis","name":"article_title","label":"Article Title"},{"value":"Nanotechnology","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2024 The Author(s). Published by IOP Publishing Ltd","name":"copyright_information","label":"Copyright Information"},{"value":"2024-05-10","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2024-08-20","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2024-09-04","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}