Acid-resistant chemotactic DNA micromotors for probiotic delivery in inflammatory bowel disease

Abstract Microcapsules composed of synthetic polymeric matrices have attracted considerable attention in delivering oral probiotics. However, existing polymeric microcapsules demonstrate inadequate acid resistance and adaptability, as well as deficiency in the inflamed colon-specificity and uncontro...

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Main Authors: Zinan Zhao, Yao Xu, Yong Hu
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59172-9
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author Zinan Zhao
Yao Xu
Yong Hu
author_facet Zinan Zhao
Yao Xu
Yong Hu
author_sort Zinan Zhao
collection DOAJ
description Abstract Microcapsules composed of synthetic polymeric matrices have attracted considerable attention in delivering oral probiotics. However, existing polymeric microcapsules demonstrate inadequate acid resistance and adaptability, as well as deficiency in the inflamed colon-specificity and uncontrolled release of probiotics therein. Herein, a DNA microcapsule is prepared as a probiotic-transporting micromotor through photo-crosslinking of hyaluronic acid methacrylate and acrydite-modified A-/C-rich oligomers within the microfludically generated droplets in the presence of nitric oxide-cleavable crosslinker and gas donor manganese carbonyl (MnCO). As the microcapsules traverse stomach, duodenum, and ultimately colon, the formation and dissociation of A-motif and i-motif structures instigate a reversible shrinking-swelling transition of microcapsules to preserve probiotic viability. Subsequently, the microcapsules exhibit chemotaxis towards inflamed colon site, driven by a gas-generating reaction between MnCO and elevated reactive oxygen species. Following disintegration of the microcapsules, triggered by endogenous nitric oxide, probiotics are released to reshape the dysbiosis of intestinal microflora. This advanced delivery system offers significant promise for the effective clinical management of inflammatory bowel disease.
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spelling doaj-art-2eecd626efa447948d288f4ca3f5511e2025-08-20T02:30:18ZengNature PortfolioNature Communications2041-17232025-04-0116112010.1038/s41467-025-59172-9Acid-resistant chemotactic DNA micromotors for probiotic delivery in inflammatory bowel diseaseZinan Zhao0Yao Xu1Yong Hu2Department of Polymeric Materials, School of Materials Science and Engineering, Tongji UniversityDepartment of Polymeric Materials, School of Materials Science and Engineering, Tongji UniversityDepartment of Polymeric Materials, School of Materials Science and Engineering, Tongji UniversityAbstract Microcapsules composed of synthetic polymeric matrices have attracted considerable attention in delivering oral probiotics. However, existing polymeric microcapsules demonstrate inadequate acid resistance and adaptability, as well as deficiency in the inflamed colon-specificity and uncontrolled release of probiotics therein. Herein, a DNA microcapsule is prepared as a probiotic-transporting micromotor through photo-crosslinking of hyaluronic acid methacrylate and acrydite-modified A-/C-rich oligomers within the microfludically generated droplets in the presence of nitric oxide-cleavable crosslinker and gas donor manganese carbonyl (MnCO). As the microcapsules traverse stomach, duodenum, and ultimately colon, the formation and dissociation of A-motif and i-motif structures instigate a reversible shrinking-swelling transition of microcapsules to preserve probiotic viability. Subsequently, the microcapsules exhibit chemotaxis towards inflamed colon site, driven by a gas-generating reaction between MnCO and elevated reactive oxygen species. Following disintegration of the microcapsules, triggered by endogenous nitric oxide, probiotics are released to reshape the dysbiosis of intestinal microflora. This advanced delivery system offers significant promise for the effective clinical management of inflammatory bowel disease.https://doi.org/10.1038/s41467-025-59172-9
spellingShingle Zinan Zhao
Yao Xu
Yong Hu
Acid-resistant chemotactic DNA micromotors for probiotic delivery in inflammatory bowel disease
Nature Communications
title Acid-resistant chemotactic DNA micromotors for probiotic delivery in inflammatory bowel disease
title_full Acid-resistant chemotactic DNA micromotors for probiotic delivery in inflammatory bowel disease
title_fullStr Acid-resistant chemotactic DNA micromotors for probiotic delivery in inflammatory bowel disease
title_full_unstemmed Acid-resistant chemotactic DNA micromotors for probiotic delivery in inflammatory bowel disease
title_short Acid-resistant chemotactic DNA micromotors for probiotic delivery in inflammatory bowel disease
title_sort acid resistant chemotactic dna micromotors for probiotic delivery in inflammatory bowel disease
url https://doi.org/10.1038/s41467-025-59172-9
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AT yonghu acidresistantchemotacticdnamicromotorsforprobioticdeliveryininflammatoryboweldisease