局部光热消融 MRSA 感染骨髓炎联合化疗的热敏纳米治疗,ACS Applied Materials & Interfaces

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局部光热消融 MRSA 感染骨髓炎联合化疗的热敏纳米治疗
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-03-02 , DOI: 10.1021/acsami.2c23312
Zhe Zhao ₁ , Yufei Zhang ₂ , Yijie Cheng ₂ , Jie Li ₂ , Wenbo Wang ₂ , Siyuan Huang ₂ , Xinlong Ma ₁ , Xinge Zhang ₂

Affiliation

慢性骨髓炎是由影响骨膜、骨骼和骨髓的细菌感染引起的炎症性骨骼疾病。耐甲氧西林金黄色葡萄球菌(MRSA) 是最常见的病原体。在坏死骨上形成的细菌生物膜对治疗 MRSA 感染的骨髓炎是一个相当大的挑战。在这里，我们开发了一种用于治疗 MRSA 感染的骨髓炎的一体式阳离子热敏纳米治疗剂 (TLCA)。制备的 TLCA 颗粒带正电且尺寸小于 230 nm，这使它们能够有效地扩散到生物膜中。纳米药物的正电荷准确靶向生物膜，随后在近红外（NIR）光照射下调节药物释放，从而有效发挥近红外光驱动的光热灭菌和化疗的协同作用。超过 80% 的抗生素在 50 °C 时突然释放，从而分散了高达 90% 的生物膜。当应用于MRSA感染的骨髓炎时，808 nm 激光照射诱导局部温度 50 °C，不仅可以消灭细菌和控制感染，还可以抑制骨组织炎症反应，显着降低 TNF-α、IL-1β 和 IL-6 水平。总之，我们构建了一种一体化的抗菌治疗方式，为慢性骨髓炎的局部治疗提供了一种新的有效策略。

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Thermosensitive Nanotherapeutics for Localized Photothermal Ablation of MRSA-Infected Osteomyelitis Combined with Chemotherapy

Chronic osteomyelitis is an inflammatory skeletal disease caused by a bacterial infection that affects the periosteum, bone, and bone marrow. Methicillin-resistant Staphylococcus aureus (MRSA) is the most common causative agent. The bacterial biofilm formed on the necrotic bone is a considerable challenge to treating MRSA-infected osteomyelitis. Here, we developed an all-in-one cationic thermosensitive nanotherapeutic (TLCA) for treating MRSA-infected osteomyelitis. The prepared TLCA particles were positively charged and <230 nm in size, which allowed them to diffuse effectively into the biofilm. The positive charges of the nanotherapeutic accurately targeted the biofilm, and it subsequently regulated the drug release under near-infrared (NIR) light irradiation, thereby efficiently exerting the synergistic effect of NIR light-driven photothermal sterilization and chemotherapy. More than 80% of the antibiotics were abruptly released at 50 °C, which dispersed the biofilm by up to 90%. When applied to MRSA-infected osteomyelitis, with a localized temperature of 50 °C induced by 808 nm laser irradiation, it not only eliminated the bacteria and controlled infection but also inhibited the bone tissue inflammatory response, significantly reducing TNF-α, IL-1β, and IL-6 levels. In conclusion, we constructed an all-in-one antimicrobial treatment modality that provides a new and effective strategy for the topical treatment of chronic osteomyelitis.

更新日期：2023-03-02

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