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Self-Homeostasis Immunoregulatory Strategy for Implant-Related Infections through Remodeling Redox Balance
ACS Nano ( IF 15.8 ) Pub Date : 2023-02-22 , DOI: 10.1021/acsnano.2c10660 Dongdong Xu 1 , Wanbo Zhu 1, 2 , Cheng Ding 1 , Jiawei Mei 2 , Jun Zhou 1 , Tao Cheng 1 , Geyong Guo 1 , Xianlong Zhang 1
ACS Nano ( IF 15.8 ) Pub Date : 2023-02-22 , DOI: 10.1021/acsnano.2c10660 Dongdong Xu 1 , Wanbo Zhu 1, 2 , Cheng Ding 1 , Jiawei Mei 2 , Jun Zhou 1 , Tao Cheng 1 , Geyong Guo 1 , Xianlong Zhang 1
Affiliation
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Implant-related infections (IRIs) are catastrophic complications after orthopedic surgery. Excess reactive oxygen species (ROS) accumulated in IRIs create a redox-imbalanced microenvironment around the implant, which severely limits the curing of IRIs by inducing biofilm formation and immune disorders. However, current therapeutic strategies commonly eliminate infection utilizing the explosive generation of ROS, which exacerbates the redox imbalance, aggravating immune disorders and promoting infection chronicity. Herein, a self-homeostasis immunoregulatory strategy based on a luteolin (Lut)-loaded copper (Cu2+)-doped hollow mesoporous organosilica nanoparticle system (Lut@Cu-HN) is designed to cure IRIs by remodeling the redox balance. In the acidic infection environment, Lut@Cu-HN is continuously degraded to release Lut and Cu2+. As both an antibacterial and immunomodulatory agent, Cu2+ kills bacteria directly and promotes macrophage pro-inflammatory phenotype polarization to activate the antibacterial immune response. Simultaneously, Lut scavenges excessive ROS to prevent the Cu2+-exacerbated redox imbalance from impairing macrophage activity and function, thus reducing Cu2+ immunotoxicity. The synergistic effect of Lut and Cu2+ confers excellent antibacterial and immunomodulatory properties to Lut@Cu-HN. As demonstrated in vitro and in vivo, Lut@Cu-HN self-regulates immune homeostasis through redox balance remodeling, ultimately facilitating IRI eradication and tissue regeneration.
中文翻译：
通过重塑氧化还原平衡的植入相关感染的自我稳态免疫调节策略
植入物相关感染 (IRI) 是骨科手术后的灾难性并发症。IRIs 中积累的过量活性氧 (ROS) 在植入物周围形成了氧化还原失衡的微环境，通过诱导生物膜形成和免疫紊乱严重限制了 IRIs 的治疗。然而，目前的治疗策略通常利用 ROS 的爆炸性产生来消除感染，这会加剧氧化还原失衡，加重免疫紊乱并促进感染慢性化。在此，一种基于木犀草素 (Lut) 载铜 (Cu 2+)-掺杂的空心介孔有机二氧化硅纳米粒子系统 (Lut@Cu-HN) 旨在通过重塑氧化还原平衡来治疗 IRIs。在酸性感染环境中，Lut@Cu-HN不断降解释放出Lut和Cu 2+。作为抗菌剂和免疫调节剂，Cu 2+直接杀灭细菌并促进巨噬细胞促炎表型极化以激活抗菌免疫反应。同时，Lut 清除过量的 ROS，防止 Cu 2+加剧的氧化还原失衡损害巨噬细胞的活性和功能，从而降低 Cu 2+ 的免疫毒性。Lut与Cu 2+的协同作用赋予 Lut@Cu-HN 优异的抗菌和免疫调节特性。正如体外和体内所证明的那样，Lut@Cu-HN 通过氧化还原平衡重塑自我调节免疫稳态，最终促进 IRI 根除和组织再生。
更新日期：2023-02-22
中文翻译：
通过重塑氧化还原平衡的植入相关感染的自我稳态免疫调节策略
植入物相关感染 (IRI) 是骨科手术后的灾难性并发症。IRIs 中积累的过量活性氧 (ROS) 在植入物周围形成了氧化还原失衡的微环境，通过诱导生物膜形成和免疫紊乱严重限制了 IRIs 的治疗。然而，目前的治疗策略通常利用 ROS 的爆炸性产生来消除感染，这会加剧氧化还原失衡，加重免疫紊乱并促进感染慢性化。在此，一种基于木犀草素 (Lut) 载铜 (Cu 2+)-掺杂的空心介孔有机二氧化硅纳米粒子系统 (Lut@Cu-HN) 旨在通过重塑氧化还原平衡来治疗 IRIs。在酸性感染环境中，Lut@Cu-HN不断降解释放出Lut和Cu 2+。作为抗菌剂和免疫调节剂，Cu 2+直接杀灭细菌并促进巨噬细胞促炎表型极化以激活抗菌免疫反应。同时，Lut 清除过量的 ROS，防止 Cu 2+加剧的氧化还原失衡损害巨噬细胞的活性和功能，从而降低 Cu 2+ 的免疫毒性。Lut与Cu 2+的协同作用赋予 Lut@Cu-HN 优异的抗菌和免疫调节特性。正如体外和体内所证明的那样，Lut@Cu-HN 通过氧化还原平衡重塑自我调节免疫稳态，最终促进 IRI 根除和组织再生。
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