Hyaluronan-Based Nanohydrogels for Targeting Intracellular S-Aureus in Human Keratinocytes
Hyaluronan-Based Nanohydrogels for Targeting Intracellular S-Aureus in Human Keratinocytes
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DOI：
10.1002/adhm.201701483
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发表时间：
2018-06-20
影响因子：
10
通讯作者：
Matricardi, Pietro
中科院分区：
文献类型：
--
作者：
Montanari, Elita;Oates, Angela;Matricardi, Pietro
金黄色葡萄球菌是最重要的人类病原体之一，经常在各种浅表和全身感染中分离到。人们越来越认识到金黄色葡萄球菌侵入角质细胞和宿主免疫细胞等宿主细胞并在其内存活的能力是导致持续感染和治疗失败的潜在因素。将抗生素掺入透明质酸-胆固醇纳米水凝胶代表了针对细胞内细菌递送治疗剂的新范例。本文介绍的工作表明，NH 快速进入人类角质形成细胞并积聚到溶酶体中。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增强，可能改变抗生素在细胞内的命运，从细胞溶胶到溶酶体。事实上，庆大霉素是一种主要在溶酶体中积累的抗生素，当被捕获到 NH 中时，显示出显着且相同的抗菌活性。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表现出优先活性，为使用基于 HA 的 NH 治疗此类皮肤感染开辟了新途径。
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.