Enhanced Nitric Oxide Delivery Through Self‐Assembling Nanoparticles for Eradicating Gram‐Negative Bacteria
In the current battle against antibiotic resistance, the resilience of Gram‐negative bacteria against traditional antibiotics is due not only to their protective outer membranes but also to mechanisms like efflux pumps and enzymatic degradation of drugs, underscores the urgent need for innovative an...
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| Veröffentlicht in: | Advanced healthcare materials 2024-12, Vol.13 (32), p.e2403046-n/a |
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| creator | Lai, Xiangfeng Yu, Lei Huang, Xiangyi Gardner, Wil Bamford, Sarah E. Pigram, Paul J. Wang, Shuhong Brun, Anton P. Le Muir, Benjamin W. Song, Jiangning Wang, Yajun Hsu, Hsien‐Yi Chan, Philip Wai Hong Shen, Hsin‐Hui |
| description | In the current battle against antibiotic resistance, the resilience of Gram‐negative bacteria against traditional antibiotics is due not only to their protective outer membranes but also to mechanisms like efflux pumps and enzymatic degradation of drugs, underscores the urgent need for innovative antimicrobial tactics. Herein, this study presents an innovative method involving the synthesis of three furoxan derivatives engineered to self‐assemble into nitric oxide (NO) donor nanoparticles (FuNPs). These FuNPs, notably supplied together with polymyxin B (PMB), achieve markedly enhanced bactericidal efficacy against a wide spectrum of bacterial phenotypes at considerably lower NO concentrations (0.1–2.8 µg mL−1), which is at least ten times lower than the reported data for NO donors (≥200 µg mL−1). The bactericidal mechanism is elucidated using confocal, scanning, and transmission electron microscopy techniques. Neutron reflectometry confirms that FuNPs initiate membrane disruption by specifically engaging with the polysaccharides on bacterial surfaces, causing structural perturbations. Subsequently, PMB binds to lipid A on the outer membrane, enhancing permeability and resulting in a synergistic bactericidal action with FuNPs. This pioneering strategy underscores the utility of self‐assembly in NO delivery as a groundbreaking paradigm to circumvent traditional antibiotic resistance barriers, marking a significant leap forward in the development of next‐generation antimicrobial agents.
This study presents an innovative approach to combat antibiotic‐resistant Gram‐negative bacteria by utilizing self‐assembling nanoparticles that deliver nitric oxide (NO). These nanoparticles, combined with polymyxin B, significantly enhance antibacterial efficacy at lower NO concentrations, disrupting bacterial membranes and reducing resistance development. The findings offer a promising pathway for next‐generation antimicrobial therapies. |
| doi_str_mv | 10.1002/adhm.202403046 |
| format | Article |
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This study presents an innovative approach to combat antibiotic‐resistant Gram‐negative bacteria by utilizing self‐assembling nanoparticles that deliver nitric oxide (NO). These nanoparticles, combined with polymyxin B, significantly enhance antibacterial efficacy at lower NO concentrations, disrupting bacterial membranes and reducing resistance development. The findings offer a promising pathway for next‐generation antimicrobial therapies.</description><identifier>ISSN: 2192-2640</identifier><identifier>ISSN: 2192-2659</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.202403046</identifier><identifier>PMID: 39263842</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Antibiotic resistance ; Antibiotics ; Antimicrobial agents ; antimicrobial resistance ; Bacteria ; bacterial membrane ; Biodegradation ; Drug resistance ; Efflux ; Gram-negative bacteria ; Gram-Negative Bacteria - drug effects ; Lipid A ; Lipids ; Membrane permeability ; Membranes ; Microbial Sensitivity Tests ; Nanoparticles ; Nanoparticles - chemistry ; neutron ; Nitric oxide ; Nitric Oxide - chemistry ; Nitric Oxide - metabolism ; Outer membranes ; Phenotypes ; Polymyxin B ; Polymyxin B - chemistry ; Polymyxin B - pharmacology ; Polysaccharides ; Self-assembly ; Transmission electron microscopy</subject><ispartof>Advanced healthcare materials, 2024-12, Vol.13 (32), p.e2403046-n/a</ispartof><rights>2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH</rights><rights>2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3546-ddb79183f10a764beeca819d45267e2dd208a5b19bf13bc839f1826566d961973</cites><orcidid>0000-0002-8541-4370</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fadhm.202403046$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadhm.202403046$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,777,781,882,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39263842$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lai, Xiangfeng</creatorcontrib><creatorcontrib>Yu, Lei</creatorcontrib><creatorcontrib>Huang, Xiangyi</creatorcontrib><creatorcontrib>Gardner, Wil</creatorcontrib><creatorcontrib>Bamford, Sarah E.</creatorcontrib><creatorcontrib>Pigram, Paul J.</creatorcontrib><creatorcontrib>Wang, Shuhong</creatorcontrib><creatorcontrib>Brun, Anton P. Le</creatorcontrib><creatorcontrib>Muir, Benjamin W.</creatorcontrib><creatorcontrib>Song, Jiangning</creatorcontrib><creatorcontrib>Wang, Yajun</creatorcontrib><creatorcontrib>Hsu, Hsien‐Yi</creatorcontrib><creatorcontrib>Chan, Philip Wai Hong</creatorcontrib><creatorcontrib>Shen, Hsin‐Hui</creatorcontrib><title>Enhanced Nitric Oxide Delivery Through Self‐Assembling Nanoparticles for Eradicating Gram‐Negative Bacteria</title><title>Advanced healthcare materials</title><addtitle>Adv Healthc Mater</addtitle><description>In the current battle against antibiotic resistance, the resilience of Gram‐negative bacteria against traditional antibiotics is due not only to their protective outer membranes but also to mechanisms like efflux pumps and enzymatic degradation of drugs, underscores the urgent need for innovative antimicrobial tactics. Herein, this study presents an innovative method involving the synthesis of three furoxan derivatives engineered to self‐assemble into nitric oxide (NO) donor nanoparticles (FuNPs). These FuNPs, notably supplied together with polymyxin B (PMB), achieve markedly enhanced bactericidal efficacy against a wide spectrum of bacterial phenotypes at considerably lower NO concentrations (0.1–2.8 µg mL−1), which is at least ten times lower than the reported data for NO donors (≥200 µg mL−1). The bactericidal mechanism is elucidated using confocal, scanning, and transmission electron microscopy techniques. Neutron reflectometry confirms that FuNPs initiate membrane disruption by specifically engaging with the polysaccharides on bacterial surfaces, causing structural perturbations. Subsequently, PMB binds to lipid A on the outer membrane, enhancing permeability and resulting in a synergistic bactericidal action with FuNPs. This pioneering strategy underscores the utility of self‐assembly in NO delivery as a groundbreaking paradigm to circumvent traditional antibiotic resistance barriers, marking a significant leap forward in the development of next‐generation antimicrobial agents.
This study presents an innovative approach to combat antibiotic‐resistant Gram‐negative bacteria by utilizing self‐assembling nanoparticles that deliver nitric oxide (NO). These nanoparticles, combined with polymyxin B, significantly enhance antibacterial efficacy at lower NO concentrations, disrupting bacterial membranes and reducing resistance development. The findings offer a promising pathway for next‐generation antimicrobial therapies.</description><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibiotic resistance</subject><subject>Antibiotics</subject><subject>Antimicrobial agents</subject><subject>antimicrobial resistance</subject><subject>Bacteria</subject><subject>bacterial membrane</subject><subject>Biodegradation</subject><subject>Drug resistance</subject><subject>Efflux</subject><subject>Gram-negative bacteria</subject><subject>Gram-Negative Bacteria - drug effects</subject><subject>Lipid A</subject><subject>Lipids</subject><subject>Membrane permeability</subject><subject>Membranes</subject><subject>Microbial Sensitivity Tests</subject><subject>Nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>neutron</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - chemistry</subject><subject>Nitric Oxide - metabolism</subject><subject>Outer membranes</subject><subject>Phenotypes</subject><subject>Polymyxin B</subject><subject>Polymyxin B - chemistry</subject><subject>Polymyxin B - pharmacology</subject><subject>Polysaccharides</subject><subject>Self-assembly</subject><subject>Transmission electron microscopy</subject><issn>2192-2640</issn><issn>2192-2659</issn><issn>2192-2659</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqFkc1uEzEYRS0EolXpliWyxIZNgv_GM16h0IYWqaQLytry2N9kXM2Mgz0TyI5H4Bl5EhylhJ8N3tjWd3zlq4PQc0rmlBD22ri2nzPCBOFEyEfolFHFZkwW6vHxLMgJOk_pnuQlCyor-hSdcMUkrwQ7RWE5tGaw4PDKj9FbfPvVO8CX0PktxB2-a2OY1i3-CF3z49v3RUrQ150f1nhlhrAxcfS2g4SbEPEyGuetGffTq2j6zK9gne9bwG-NHSF68ww9aUyX4PxhP0Of3i3vLq5nN7dX7y8WNzPLCyFnztWlohVvKDGlFDWANRVVThRMlsCcY6QyRU1V3VBe24qrhla5uJROSapKfobeHHI3U92DszCM0XR6E31v4k4H4_Xfk8G3eh22mlJZElbuE149JMTweYI06t4nC11nBghT0pwSLgoqFM_oy3_Q-zDFIffLlFDZEC2KTM0PlI0hpQjN8TeU6L1Pvfepjz7zgxd_djjiv-xlQB2AL76D3X_i9OLy-sPv8J_4W673</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Lai, Xiangfeng</creator><creator>Yu, Lei</creator><creator>Huang, Xiangyi</creator><creator>Gardner, Wil</creator><creator>Bamford, Sarah E.</creator><creator>Pigram, Paul J.</creator><creator>Wang, Shuhong</creator><creator>Brun, Anton P. 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Le</au><au>Muir, Benjamin W.</au><au>Song, Jiangning</au><au>Wang, Yajun</au><au>Hsu, Hsien‐Yi</au><au>Chan, Philip Wai Hong</au><au>Shen, Hsin‐Hui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhanced Nitric Oxide Delivery Through Self‐Assembling Nanoparticles for Eradicating Gram‐Negative Bacteria</atitle><jtitle>Advanced healthcare materials</jtitle><addtitle>Adv Healthc Mater</addtitle><date>2024-12</date><risdate>2024</risdate><volume>13</volume><issue>32</issue><spage>e2403046</spage><epage>n/a</epage><pages>e2403046-n/a</pages><issn>2192-2640</issn><issn>2192-2659</issn><eissn>2192-2659</eissn><abstract>In the current battle against antibiotic resistance, the resilience of Gram‐negative bacteria against traditional antibiotics is due not only to their protective outer membranes but also to mechanisms like efflux pumps and enzymatic degradation of drugs, underscores the urgent need for innovative antimicrobial tactics. Herein, this study presents an innovative method involving the synthesis of three furoxan derivatives engineered to self‐assemble into nitric oxide (NO) donor nanoparticles (FuNPs). These FuNPs, notably supplied together with polymyxin B (PMB), achieve markedly enhanced bactericidal efficacy against a wide spectrum of bacterial phenotypes at considerably lower NO concentrations (0.1–2.8 µg mL−1), which is at least ten times lower than the reported data for NO donors (≥200 µg mL−1). The bactericidal mechanism is elucidated using confocal, scanning, and transmission electron microscopy techniques. Neutron reflectometry confirms that FuNPs initiate membrane disruption by specifically engaging with the polysaccharides on bacterial surfaces, causing structural perturbations. Subsequently, PMB binds to lipid A on the outer membrane, enhancing permeability and resulting in a synergistic bactericidal action with FuNPs. This pioneering strategy underscores the utility of self‐assembly in NO delivery as a groundbreaking paradigm to circumvent traditional antibiotic resistance barriers, marking a significant leap forward in the development of next‐generation antimicrobial agents.
This study presents an innovative approach to combat antibiotic‐resistant Gram‐negative bacteria by utilizing self‐assembling nanoparticles that deliver nitric oxide (NO). These nanoparticles, combined with polymyxin B, significantly enhance antibacterial efficacy at lower NO concentrations, disrupting bacterial membranes and reducing resistance development. The findings offer a promising pathway for next‐generation antimicrobial therapies.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>39263842</pmid><doi>10.1002/adhm.202403046</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-8541-4370</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Antibiotic resistance Antibiotics Antimicrobial agents antimicrobial resistance Bacteria bacterial membrane Biodegradation Drug resistance Efflux Gram-negative bacteria Gram-Negative Bacteria - drug effects Lipid A Lipids Membrane permeability Membranes Microbial Sensitivity Tests Nanoparticles Nanoparticles - chemistry neutron Nitric oxide Nitric Oxide - chemistry Nitric Oxide - metabolism Outer membranes Phenotypes Polymyxin B Polymyxin B - chemistry Polymyxin B - pharmacology Polysaccharides Self-assembly Transmission electron microscopy |
| title | Enhanced Nitric Oxide Delivery Through Self‐Assembling Nanoparticles for Eradicating Gram‐Negative Bacteria |
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