Staphylococcus aureus is one of the most significant human pathogens that is frequently isolated in a wide range of superficial and systemic infections. The ability of S. aureus to invade and survive within host cells such as keratinocytes and host immune cells has been increasingly recognized as a potential factor in persistent infections and treatment failures. The incorporation of antibiotics into hyaluronan‐cholesterol nanohydrogels represents a novel paradigm in the delivery of therapeutic agents against intracellular bacteria. The work presented herein shows that NHs quickly enter human keratinocytes and accumulate into lysosomes. When used for targeting intracellular S. aureus the antimicrobial activity of loaded levofloxacin is enhanced, possibly changing the antibiotic intracellular fate from cytosol to lysosome. Indeed, gentamicin, an antibiotic that predominantly accumulates in lysosomes, shows significant and equal antibacterial activity when entrapped into NHs. These results strongly suggest that lysosomal formulations may display preferential activity toward intracellular S. aureus, opening new avenues for the use of HA‐based NHs for treatment of such skin infections.

中文翻译：

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基于透明质酸的纳米水凝胶靶向人类角质形成细胞内的金黄色葡萄球菌

金黄色葡萄球菌是最重要的人类病原体之一，经常在广泛的浅表和全身感染中分离出来。金黄色葡萄球菌侵入宿主细胞（例如角质形成细胞和宿主免疫细胞）并在其中存活的能力已被越来越多地视为持续感染和治疗失败的潜在因素。透明质酸-胆固醇纳米水凝胶中掺入抗生​​素代表了针对细胞内细菌的治疗剂传递的新范式。本文介绍的工作表明，NHs迅速进入人角质形成细胞并积累为溶酶体。当用于靶向细胞内金黄色葡萄球菌时负载的左氧氟沙星的抗菌活性得到增强，可能会将抗生素的细胞内命运从胞浆变为溶酶体。的确，庆大霉素是一种主要在溶酶体中积累的抗生素，当被包埋在NHs中时显示出显着且相等的抗菌活性。这些结果强烈表明，溶酶体制剂可能对细胞内金黄色葡萄球菌显示出优先活性，为使用基于HA的NHs治疗此类皮肤感染开辟了新途径。