Clearance of Intracellular Pathogens with Hyaluronic Acid Nanomicelles Responsive to H<sub>2</sub>S and pH

Hyaluronic acid (HA) is an acidic mucopolysaccharide of animal origin composed of repeating disaccharide units of N-acetylglucosamine and glucuronic acid. Due to its excellent biocompatibility, biodegradability, and selective affinity for CD44 receptors on cell surfaces, HA is widely employed as a d...

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Main Authors: Jun Luo, Hui Huang, Junfeng Jiang, Wenyu Zheng, Peng Chen, Hongjin Bai
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/29/24/5971
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author Jun Luo
Hui Huang
Junfeng Jiang
Wenyu Zheng
Peng Chen
Hongjin Bai
author_facet Jun Luo
Hui Huang
Junfeng Jiang
Wenyu Zheng
Peng Chen
Hongjin Bai
author_sort Jun Luo
collection DOAJ
description Hyaluronic acid (HA) is an acidic mucopolysaccharide of animal origin composed of repeating disaccharide units of N-acetylglucosamine and glucuronic acid. Due to its excellent biocompatibility, biodegradability, and selective affinity for CD44 receptors on cell surfaces, HA is widely employed as a drug carrier. In our study, we aimed to target subcellular bacteria by grafting cystamine onto HA scaffolds through an amide reaction, producing a linker responsive to H<sub>2</sub>S and pH changes. Subsequently, hydrophobic dodecylamine was attached to HA, forming amphiphilic molecules. These amphiphilic entities can self-assemble into nanomicelles in an aqueous solution, thereby encapsulating the antibacterial agent triclosan (TCS). The resulting HA-based system (HASS-TCS) can be internalized via CD44-mediated endocytosis, releasing substantial amounts of streptomycin and TCS in H<sub>2</sub>S-rich and acidic environments. Additionally, HASS-TCS has demonstrated effectiveness in eradicating biofilms and addressing intracellular infections caused by <i>Salmonella</i>. This study underscores a novel pH-sensitive hyaluronic acid-based drug delivery system with significant potential for the effective treatment of intracellular infections.
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spelling doaj-art-dcfd41c4846346d5b4fa4ba777a9dbe72024-12-27T14:42:48ZengMDPI AGMolecules1420-30492024-12-012924597110.3390/molecules29245971Clearance of Intracellular Pathogens with Hyaluronic Acid Nanomicelles Responsive to H<sub>2</sub>S and pHJun Luo0Hui Huang1Junfeng Jiang2Wenyu Zheng3Peng Chen4Hongjin Bai5Engineering Laboratory of Chemical Resources Utilization in South Xinjiang, Tarim University, Alar 843300, ChinaEngineering Laboratory of Chemical Resources Utilization in South Xinjiang, Tarim University, Alar 843300, ChinaEngineering Laboratory of Chemical Resources Utilization in South Xinjiang, Tarim University, Alar 843300, ChinaEngineering Laboratory of Chemical Resources Utilization in South Xinjiang, Tarim University, Alar 843300, ChinaEngineering Laboratory of Chemical Resources Utilization in South Xinjiang, Tarim University, Alar 843300, ChinaEngineering Laboratory of Chemical Resources Utilization in South Xinjiang, Tarim University, Alar 843300, ChinaHyaluronic acid (HA) is an acidic mucopolysaccharide of animal origin composed of repeating disaccharide units of N-acetylglucosamine and glucuronic acid. Due to its excellent biocompatibility, biodegradability, and selective affinity for CD44 receptors on cell surfaces, HA is widely employed as a drug carrier. In our study, we aimed to target subcellular bacteria by grafting cystamine onto HA scaffolds through an amide reaction, producing a linker responsive to H<sub>2</sub>S and pH changes. Subsequently, hydrophobic dodecylamine was attached to HA, forming amphiphilic molecules. These amphiphilic entities can self-assemble into nanomicelles in an aqueous solution, thereby encapsulating the antibacterial agent triclosan (TCS). The resulting HA-based system (HASS-TCS) can be internalized via CD44-mediated endocytosis, releasing substantial amounts of streptomycin and TCS in H<sub>2</sub>S-rich and acidic environments. Additionally, HASS-TCS has demonstrated effectiveness in eradicating biofilms and addressing intracellular infections caused by <i>Salmonella</i>. This study underscores a novel pH-sensitive hyaluronic acid-based drug delivery system with significant potential for the effective treatment of intracellular infections.https://www.mdpi.com/1420-3049/29/24/5971hyaluronic acidpH and H<sub>2</sub>S dual-responsiveintracellular bacteriabiofilm
spellingShingle Jun Luo
Hui Huang
Junfeng Jiang
Wenyu Zheng
Peng Chen
Hongjin Bai
Clearance of Intracellular Pathogens with Hyaluronic Acid Nanomicelles Responsive to H<sub>2</sub>S and pH
Molecules
hyaluronic acid
pH and H<sub>2</sub>S dual-responsive
intracellular bacteria
biofilm
title Clearance of Intracellular Pathogens with Hyaluronic Acid Nanomicelles Responsive to H<sub>2</sub>S and pH
title_full Clearance of Intracellular Pathogens with Hyaluronic Acid Nanomicelles Responsive to H<sub>2</sub>S and pH
title_fullStr Clearance of Intracellular Pathogens with Hyaluronic Acid Nanomicelles Responsive to H<sub>2</sub>S and pH
title_full_unstemmed Clearance of Intracellular Pathogens with Hyaluronic Acid Nanomicelles Responsive to H<sub>2</sub>S and pH
title_short Clearance of Intracellular Pathogens with Hyaluronic Acid Nanomicelles Responsive to H<sub>2</sub>S and pH
title_sort clearance of intracellular pathogens with hyaluronic acid nanomicelles responsive to h sub 2 sub s and ph
topic hyaluronic acid
pH and H<sub>2</sub>S dual-responsive
intracellular bacteria
biofilm
url https://www.mdpi.com/1420-3049/29/24/5971
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