Thiolated Hyaluronic Acid: A Gateway for Targeted Killing of Staphylococcus aureus on the Race for Surface Colonization.

IF 9.6 2区医学 Q1 ENGINEERING, BIOMEDICAL

Advanced Healthcare Materials Pub Date : 2025-09-12 DOI:10.1002/adhm.202502890

Mariana Blanco Massani, Susanne Meile, Annabelle Knoll, David Gintsburg, Ilaria Polidori, Anna Seybold, Débora C Coraça-Huber, Martin J Loessner, Gergely Kali, Mathias Schmelcher, Szczepan Zapotoczny, Andreas Bernkop-Schnürch

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引用次数: 0

Abstract

Hyaluronic acid (HA) is degraded by Staphylococcal hyaluronate lyase (Hysa) and mammalian hyaluronidase (Hyal). Thiolated HA (HAMS) is used as a targeted gateway for Staphylococcus aureus killing while enhancing the previous M23 endolysin-polyphosphate (M23-PP NPs) enzyme-responsive nanoparticle formulation. Synthesis of HAMS and characterization for nuclear magnetic resonance, solubility, thiol content, pKa, and degradation by Hysa and Hyal are presented. Nanoparticles prepared via ionotropic gelation between M23-PP NPs and either HAMS or HA yield M23-PP/HAMS or M23-PP/HA NPs, respectively. Their characterization includes size, zeta potential, morphology, release profiles, safety, targeted release, and efficacy. HAMS with a thiol content of 250.18 ± 90.32 µmol g^-1, solubility of 50.99 ± 0.02 mg mL^-1, exhibits pKa values of 3.2, 4.2, and 8.8. This thiolated polymer irreversibly inhibits Hyal activity, without affecting Hysa. M23-PP/HAMS NPs (265 ± 47 nm, -25 mV) maintain their integrity for seven days at 37 °C, and HAMS coating prevents nonspecific degradation by Hyal, as confirmed by release studies. In a co-culture 'race for the surface' experiment with MC3T3 osteoblasts and S. aureus ATCC 25923, M23-PP/HAMS NPs produce 8-log bacterial killing while promoting in vitro wound healing. These findings are pivotal to the development of new enzyme-responsive excipients switchable by S. aureus.

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硫代透明质酸：一种靶向杀死金黄色葡萄球菌表面定植的途径。

透明质酸（HA）被葡萄球菌透明质酸裂解酶（Hysa）和哺乳动物透明质酸酶（Hyal）降解。巯基化透明质酸（HAMS）被用作金黄色葡萄球菌杀伤的靶向通道，同时增强了先前的M23内溶素-聚磷酸酯（M23- pp NPs）酶反应纳米颗粒配方。介绍了其合成、核磁共振、溶解度、硫醇含量、pKa、Hysa和Hyal降解等方面的表征。在M23-PP NPs与HAMS或HA之间通过离子化胶凝制备纳米颗粒，分别得到M23-PP/HAMS或M23-PP/HA NPs。它们的特性包括大小、zeta电位、形态、释放谱、安全性、靶向释放和有效性。硫醇含量为250.18±90.32µmol g-1，溶解度为50.99±0.02 mg mL-1，其pKa值分别为3.2、4.2和8.8。这种硫代聚合物不可逆地抑制Hyal活性，而不影响Hysa。释放研究证实，M23-PP/HAMS NPs（265±47 nm, -25 mV）在37°C下可保持7天的完整性，并且HAMS涂层可防止Hyal的非特异性降解。在MC3T3成骨细胞和金黄色葡萄球菌ATCC 25923共培养的“表面竞赛”实验中，M23-PP/HAMS NPs在促进体外伤口愈合的同时产生8倍的细菌杀伤。这些发现对于开发可由金黄色葡萄球菌切换的新型酶反应赋形剂至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advanced Healthcare Materials 工程技术-生物材料

CiteScore

14.40

自引率

3.00%

发文量

600

审稿时长

1.8 months

期刊介绍： Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.