碱性“纳米剑”协调铁死亡样细菌死亡以实现抗菌和骨整合,ACS Nano

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碱性“纳米剑”协调铁死亡样细菌死亡以实现抗菌和骨整合
ACS Nano ( IF 15.8 ) Pub Date : 2023-01-20 , DOI: 10.1021/acsnano.2c10960
Yang Xue ₁ , Lan Zhang ₁ , Fuwei Liu ₂ , Fang Dai ₁ , Liang Kong ₂ , Dayan Ma ₁ , Yong Han ₁

Affiliation

铁死亡是一种铁依赖性细胞死亡，与癌症治疗有关。它能否在抵抗植入物术后感染方面发挥作用，特别是在非细胞毒性剂量的细胞外补充铁离子？为了回答这个问题，在 Ti 植入物表面制造了掺杂 Fe 的钛酸盐“纳米剑”，通过类铁死亡细菌杀灭、质子扰动和物理穿刺的协同作用来抵抗细菌入侵。通过原子力显微镜和基因组测序探索相关的抗菌机制。纳米剑诱导局部pH值升高，这不仅削弱了质子动力，减少了金黄色葡萄球菌的三磷酸腺苷合成，但也会降低膜模量，使纳米剑变形甚至容易刺穿细菌膜。同时，由于细菌膜通透性增加，细菌吸收更多的铁离子，导致细菌铁死亡样死亡，这表现为细胞内铁富集、脂质过氧化和谷胱甘肽耗竭。有趣的是，由这些纳米剑构建的微环境改善了体外成骨细胞的行为和体内的骨再生。总的来说，纳米剑可以诱导类似铁死亡的细菌死亡而没有细胞毒性，并且在临床植入物的应用中具有出色的抗菌和生物整合性能。

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Alkaline “Nanoswords” Coordinate Ferroptosis-like Bacterial Death for Antibiosis and Osseointegration

Ferroptosis is an iron-dependent cell death and is associated with cancer therapy. Can it play a role in resistance of postoperative infection of implants, especially with an extracellular supplement of Fe ions in a non-cytotoxic dose? To answer this, “nanoswords” of Fe-doped titanite are fabricated on a Ti implant surface to resist bacterial invasion by a synergistic action of ferroptosis-like bacteria killing, proton disturbance, and physical puncture. The related antibiosis mechanism is explored by atomic force microscopy and genome sequencing. The nanoswords induce an increased local pH value, which not only weakens the proton motive force, reducing adenosine triphosphate synthesis of Staphylococcus aureus, but also decreases the membrane modulus, making the nanoswords distort and even puncture a bacterial membrane easily. Simultaneously, more Fe ions are taken by bacteria due to increased bacterial membrane permeability, resulting in ferroptosis-like death of bacteria, and this is demonstrated by intracellular iron enrichment, lipid peroxidation, and glutathione depletion. Interestingly, a microenvironment constructed by these nanoswords improves osteoblast behavior in vitro and bone regeneration in vivo. Overall, the nanoswords can induce ferroptosis-like bacterial death without cytotoxicity and have great promise in applications with clinical implants for outstanding antibiosis and biointegration performance.

更新日期：2023-01-20

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