Mild-Temperature Photothermal Effect Triggers Simultaneous Nitric Oxide- and Deferoxamine-Releasing Mesoporous Polydopamine-Based Nanoplatform for Robust Antibacterial, Anti-inflammation, and Wound-Healing Activity
Mild-Temperature Photothermal Effect Triggers Simultaneous Nitric Oxide- and Deferoxamine-Releasing Mesoporous Polydopamine-Based Nanoplatform for Robust Antibacterial, Anti-inflammation, and Wound-Healing Activity
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DOI：
10.1021/acs.chemmater.2c02686
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发表时间：
2022-12
影响因子：
8.6
通讯作者：
Wenkang Liu;Xiling Song;W. Liu;Qianming Lin;R. Xu;Hui Li;Wei Xue;Siming Yu
中科院分区：
文献类型：
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作者：
Wenkang Liu;Xiling Song;W. Liu;Qianming Lin;R. Xu;Hui Li;Wei Xue;Siming Yu
目前，慢性感染伤口的治疗仍然是一个巨大的挑战;因此，迫切需要一种具有高效治疗效果的新策略。在目前的工作中，我们证明了一氧化氮（NO）和去铁胺（DFO）的组合使用是一种很有前途的方法来治疗难以愈合的伤口。作为概念验证，首先将DFO负载于介孔聚多巴胺（mPDA）中，然后通过强静电相互作用将其与具有末端S-亚硝基硫醇基团的壳聚糖-接枝-第三代聚（酰胺-胺）聚合物（CP-SNO）官能化，得到多功能纳米复合材料mPDA@DFO@CP-SNO。在近红外激光照射下，mPDA@DFO@CP-SNO表现出温和的光热效应（MPTT），并具有NO和DFO同时控释的特性。mPDA@DFO@CP-SNO的协同MPTT和NO抗菌作用使其能够有效地消除革兰氏阴性大肠杆菌和革兰氏阳性金黄色葡萄球菌（S.金黄色葡萄球菌），以及由这两种细菌形成的生物膜。深入的机理研究表明，mPDA@DFO@CP-SNO对细菌细胞膜具有特殊的结合亲和力，可显著增强对细菌细胞膜的损伤作用，进而促进细胞内活性氧的产生，加速GSH耗竭和DNA功能障碍，最终导致细菌死亡。此外，mPDA@DFO@CP-SNO在体外细胞划痕模型和动物体内的抗炎和伤口愈合效果得到证实。金黄色葡萄球菌感染的大鼠全层皮肤伤口模型。mPDA@DFO@CP-SNO具有MPTT、DFO和NO的三重治疗作用，通过上调缺氧诱导因子（HIF）-1α和血管内皮生长因子（VEGF）的表达，显著减轻大鼠感染创面的炎症反应，促进创面皮肤再生。
Currently, treatment of chronically infected wounds still remains a big challenge; thus, a novel strategy with a highly efficient therapeutic effect is of urgent demand. In the present work, we demonstrated that combinational use of nitric oxide (NO) and deferoxamine (DFO) is a promising way for treating hard-to-heal wounds. As a proof of concept, DFO was first loaded in mesoporous polydopamine (mPDA) and then functionalized by a chitosan-graft-third generation poly(amidoamine) polymer with terminalS-nitrosothiol groups (CP-SNO)viaa strong electrostatic interaction, obtaining a multifunctional nanocomposite mPDA@DFO@CP-SNO. Upon near-infrared laser irradiation, mPDA@DFO@CP-SNO displayed a mild-temperature photothermal effect (MPTT) and a simultaneous NO and DFO controlled release property. The synergistic MPTT and NO antibacterial effect of mPDA@DFO@CP-SNO enabled effective elimination of both Gram-negativeEscherichia coliand Gram-positiveStaphylococcus aureus(S. aureus), as well as the biofilms formed by both bacteria. An in-depth mechanistic study revealed that mPDA@DFO@CP-SNO possessed particular binding affinity to the bacterial membrane, which significantly enhanced the damage effect on the bacterial membrane followed by boosting intracellular reactive oxygen species generation to accelerate GSH depletion and DNA dysfunction, finally leading to bacterial death. Moreover, the anti-inflammation and wound-healing effectiveness of mPDA@DFO@CP-SNO were demonstrated on anin vitrocell scratch model and anin vivoS. aureus-infected rat full-thickness skin wound model. Thanks to the triple therapeutic effects of MPTT, DFO, and NO, mPDA@DFO@CP-SNO significantly relieved the inflammation in rats’ infected wounds and promoted wound skin regeneration by upregulating expression of the hypoxia-inducible factor (HIF)-1α and the vascular endothelial growth factor.