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Localized pH regulation via a dynamic proton-converting raft for gastroesophageal reflux disease.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Localized pH regulation via a dynamic proton-converting raft for gastroesophageal reflux disease.
Συγγραφείς: Li Y; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China., Yang Y; Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research, Ministry of Education, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081, China. Electronic address: yanxiayang@hunnu.edu.cn., Zhao W; Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China., Ren Z; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China., Zhang N; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China., Cao X; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China., Dong Q; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China., Bao M; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China., Lv Z; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China., Li Z; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China., Lin C; Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China. Electronic address: linchangwei@csu.edu.cn., Ding D; Institute of Molecular Medicine (IMM), Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China. Electronic address: Dding@sjtu.edu.cn., Chen Z; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China. Electronic address: zhuochen@hnu.edu.cn.
Πηγή: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2026 Sep 10; Vol. 397, pp. 115162. Date of Electronic Publication: 2026 Jul 06.
Τύπος έκδοσης: Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE
Imprint Name(s): Original Publication: Amsterdam : Elsevier Science Publishers, 1984-
Ιατρικοί όροι (MeSH): Alginates*/chemistry , Alginates*/administration & dosage , Gastroesophageal Reflux*/drug therapy , Gastroesophageal Reflux*/metabolism , Urease*/metabolism , Urease*/genetics, Hexuronic Acids/chemistry ; Hexuronic Acids/administration & dosage ; Lactococcus lactis/genetics ; Lactococcus lactis/enzymology ; Glucuronic Acid/chemistry ; Glucuronic Acid/administration & dosage ; Carbon Dioxide/metabolism ; Animals ; Hydrogen-Ion Concentration ; Protons ; Rats, Sprague-Dawley
Περίληψη: Current gastroesophageal reflux disease (GERD) therapies either systemically suppress gastric acid, risking physiological disruption, or rely on antacid rafts that offer transient, non-responsive neutralization. We address this with a chemistry-centered strategy that spatially localizes proton conversion around the self-positioning raft at the gastric interface. The dynamic H+ conversion equilibrium system (DH+-CES) integrates a CO2-generating calcium alginate raft which physically impedes reflux via its bubble-stabilized architecture for rapid interfacial self-positioning, with an engineered Lactococcus lactis expressing acid urease. Under acidic challenge, urease catalysis consumes protons locally. As pH normalizes, feedback-regulated enzymatic attenuation constrains the reaction zone, preventing bulk alkalization. DH+-CES elevates interfacial pH from 2.0 to ∼5.0 within 5 min, sustains this zone for hours while modulating only 5.38% of total fluid volume, and reduces reflux-like surge height by 38%. In an acute rat GERD model, it inhibits esophageal injury by 93.95%, downregulates key inflammatory mediators, and shows favorable biocompatibility. These findings establish DH+-CES as a proof-of-concept interface-resident chemical gatekeeper for localized, self-limiting, and physiologically respectful pH control.
(Copyright © 2026 Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare no competing interests.
Contributed Indexing: Keywords: Dynamic H(+) conversion; Engineered bacteria; Enzyme catalysis; Floating alginate raft; Gels
Substance Nomenclature: 0 (Alginates)
0 (Protons)
EC 3.5.1.5 (Urease)
0 (Hexuronic Acids)
8A5D83Q4RW (Glucuronic Acid)
142M471B3J (Carbon Dioxide)
Entry Date(s): Date Created: 20260706 Date Completed: 20260826 Latest Revision: 20260907
Update Code: 20260907
DOI: 10.1016/j.jconrel.2026.115162
PMID: 42409243
Βάση Δεδομένων: MEDLINE
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  Data: Localized pH regulation via a dynamic proton-converting raft for gastroesophageal reflux disease.
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  Data: <searchLink fieldCode="AU" term="%22Li+Y%22">Li Y</searchLink>; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.<br /><searchLink fieldCode="AU" term="%22Yang+Y%22">Yang Y</searchLink>; Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research, Ministry of Education, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081, China. Electronic address: yanxiayang@hunnu.edu.cn.<br /><searchLink fieldCode="AU" term="%22Zhao+W%22">Zhao W</searchLink>; Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China.<br /><searchLink fieldCode="AU" term="%22Ren+Z%22">Ren Z</searchLink>; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.<br /><searchLink fieldCode="AU" term="%22Zhang+N%22">Zhang N</searchLink>; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.<br /><searchLink fieldCode="AU" term="%22Cao+X%22">Cao X</searchLink>; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.<br /><searchLink fieldCode="AU" term="%22Dong+Q%22">Dong Q</searchLink>; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.<br /><searchLink fieldCode="AU" term="%22Bao+M%22">Bao M</searchLink>; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.<br /><searchLink fieldCode="AU" term="%22Lv+Z%22">Lv Z</searchLink>; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.<br /><searchLink fieldCode="AU" term="%22Li+Z%22">Li Z</searchLink>; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.<br /><searchLink fieldCode="AU" term="%22Lin+C%22">Lin C</searchLink>; Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China. Electronic address: linchangwei@csu.edu.cn.<br /><searchLink fieldCode="AU" term="%22Ding+D%22">Ding D</searchLink>; Institute of Molecular Medicine (IMM), Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China. Electronic address: Dding@sjtu.edu.cn.<br /><searchLink fieldCode="AU" term="%22Chen+Z%22">Chen Z</searchLink>; Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and BioSensing, College of Chemistry and Chemical Engineering, College of Environmental Science and Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China. Electronic address: zhuochen@hnu.edu.cn.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Elsevier+Science+Publishers%22">Elsevier Science Publishers </searchLink><i>Country of Publication: </i>Netherlands <i>NLM ID: </i>8607908 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1873-4995 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2201683659%22">01683659 </searchLink><i>NLM ISO Abbreviation: </i>J Control Release <i>Subsets: </i>MEDLINE
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  Data: <i>Original Publication</i>: Amsterdam : Elsevier Science Publishers, 1984-
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  Data: <searchLink fieldCode="MM" term="%22Alginates%22">Alginates*</searchLink>/<searchLink fieldCode="MM" term="%22Alginates+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Alginates%22">Alginates*</searchLink>/<searchLink fieldCode="MM" term="%22Alginates+administration+%26+dosage%22">administration & dosage</searchLink> <br /><searchLink fieldCode="MM" term="%22Gastroesophageal+Reflux%22">Gastroesophageal Reflux*</searchLink>/<searchLink fieldCode="MM" term="%22Gastroesophageal+Reflux+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Gastroesophageal+Reflux%22">Gastroesophageal Reflux*</searchLink>/<searchLink fieldCode="MM" term="%22Gastroesophageal+Reflux+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Urease%22">Urease*</searchLink>/<searchLink fieldCode="MM" term="%22Urease+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Urease%22">Urease*</searchLink>/<searchLink fieldCode="MM" term="%22Urease+genetics%22">genetics</searchLink><br /><searchLink fieldCode="MH" term="%22Hexuronic+Acids%22">Hexuronic Acids</searchLink>/<searchLink fieldCode="MH" term="%22Hexuronic+Acids+chemistry%22">chemistry</searchLink> ; <searchLink fieldCode="MH" term="%22Hexuronic+Acids%22">Hexuronic Acids</searchLink>/<searchLink fieldCode="MH" term="%22Hexuronic+Acids+administration+%26+dosage%22">administration & dosage</searchLink> ; <searchLink fieldCode="MH" term="%22Lactococcus+lactis%22">Lactococcus lactis</searchLink>/<searchLink fieldCode="MH" term="%22Lactococcus+lactis+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Lactococcus+lactis%22">Lactococcus lactis</searchLink>/<searchLink fieldCode="MH" term="%22Lactococcus+lactis+enzymology%22">enzymology</searchLink> ; <searchLink fieldCode="MH" term="%22Glucuronic+Acid%22">Glucuronic Acid</searchLink>/<searchLink fieldCode="MH" term="%22Glucuronic+Acid+chemistry%22">chemistry</searchLink> ; <searchLink fieldCode="MH" term="%22Glucuronic+Acid%22">Glucuronic Acid</searchLink>/<searchLink fieldCode="MH" term="%22Glucuronic+Acid+administration+%26+dosage%22">administration & dosage</searchLink> ; <searchLink fieldCode="MH" term="%22Carbon+Dioxide%22">Carbon Dioxide</searchLink>/<searchLink fieldCode="MH" term="%22Carbon+Dioxide+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Hydrogen-Ion+Concentration%22">Hydrogen-Ion Concentration</searchLink> ; <searchLink fieldCode="MH" term="%22Protons%22">Protons</searchLink> ; <searchLink fieldCode="MH" term="%22Rats%2C+Sprague-Dawley%22">Rats, Sprague-Dawley</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Current gastroesophageal reflux disease (GERD) therapies either systemically suppress gastric acid, risking physiological disruption, or rely on antacid rafts that offer transient, non-responsive neutralization. We address this with a chemistry-centered strategy that spatially localizes proton conversion around the self-positioning raft at the gastric interface. The dynamic H<superscript>+</superscript> conversion equilibrium system (DH<superscript>+</superscript>-CES) integrates a CO<subscript>2</subscript>-generating calcium alginate raft which physically impedes reflux via its bubble-stabilized architecture for rapid interfacial self-positioning, with an engineered Lactococcus lactis expressing acid urease. Under acidic challenge, urease catalysis consumes protons locally. As pH normalizes, feedback-regulated enzymatic attenuation constrains the reaction zone, preventing bulk alkalization. DH<superscript>+</superscript>-CES elevates interfacial pH from 2.0 to ∼5.0 within 5 min, sustains this zone for hours while modulating only 5.38% of total fluid volume, and reduces reflux-like surge height by 38%. In an acute rat GERD model, it inhibits esophageal injury by 93.95%, downregulates key inflammatory mediators, and shows favorable biocompatibility. These findings establish DH<superscript>+</superscript>-CES as a proof-of-concept interface-resident chemical gatekeeper for localized, self-limiting, and physiologically respectful pH control.<br /> (Copyright © 2026 Elsevier B.V. All rights reserved.)
– Name: Abstract
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  Data: Declaration of competing interest The authors declare no competing interests.
– Name: SubjectMinor
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  Data: <i>Keywords: </i>Dynamic H(+) conversion; Engineered bacteria; Enzyme catalysis; Floating alginate raft; Gels
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  Data: 0 (Alginates)<br />0 (Protons)<br />EC 3.5.1.5 (Urease)<br />0 (Hexuronic Acids)<br />8A5D83Q4RW (Glucuronic Acid)<br />142M471B3J (Carbon Dioxide)
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  Data: <i>Date Created: </i>20260706 <i>Date Completed: </i>20260826 <i>Latest Revision: </i>20260907
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  Data: 10.1016/j.jconrel.2026.115162
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        Value: 10.1016/j.jconrel.2026.115162
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        Text: English
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        StartPage: 115162
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      – SubjectFull: Hexuronic Acids chemistry
        Type: general
      – SubjectFull: Hexuronic Acids administration & dosage
        Type: general
      – SubjectFull: Lactococcus lactis genetics
        Type: general
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      – SubjectFull: Gastroesophageal Reflux drug therapy
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        Type: general
      – SubjectFull: Urease metabolism
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