Shi Tingwang, Ruan Zesong, Wang Xin, Lian Xiaofeng, Chen Yunfeng
Department of Orthopedic Surgery, and Shanghai Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P. R. China.
J Mater Chem B. 2022 Mar 16;10(11):1805-1820. doi: 10.1039/d1tb02615a.
Implant-related infections (IRIs) caused by bacterial biofilms remain a prevalent but tricky clinical issue, and are characterized by drug resistance, toxin impairment and immunosuppression. Recently, reactive oxygen species (ROS)- and hyperthermia-based antimicrobial therapies have been developed to effectively destroy biofilms. However, almost all of them have failed to simultaneously focus on the immunosuppressive biofilm microenvironment and bacterial toxin-induced tissue damage. Herein, we proposed a one-arrow-three-hawks strategy to orchestrate hyperthermia/ROS antibiofilm therapy, toxin neutralization and immunomodulatory therapy through engineering a bioinspired erythrocyte membrane-enveloped molybdenum disulfide nanodot (EM@MoS) nanoplatform. In the biofilm microenvironment, pore-forming toxins actively attack the erythrocyte membranes on the nanodots and are detained, thus staying away from their targets and mitigating tissue damage. Under near-infrared (NIR) laser irradiation, MoS nanodots, with superb photothermal and peroxidase (POD)-like properties, exert a powerful synergistic antibiofilm effect. More intriguingly, we initially identified that they possessed the ability to reverse the immunosuppressive microenvironment by skewing the macrophages from an anti-inflammatory phenotype to a proinflammatory phenotype, which would promote the elimination of biofilm debris and prevent infection relapse. Systematic and evaluations have demonstrated that EM@MoS achieves a remarkable antibiofilm effect. The current study integrated the functions of hyperthermia/ROS therapy, virulence clearance and immune regulation, which could provide an effective paradigm for IRIs therapy.
由细菌生物膜引起的植入物相关感染（IRI）仍然是一个普遍但棘手的临床问题，其特征是耐药性、毒素损伤和免疫抑制。最近，基于活性氧（ROS）和热疗的抗菌疗法已被开发出来，以有效破坏生物膜。然而，几乎所有这些疗法都未能同时关注免疫抑制性生物膜微环境和细菌毒素诱导的组织损伤。在此，我们提出了一种一箭三雕的策略，通过构建一种受生物启发的红细胞膜包裹的二硫化钼纳米点（EM@MoS）纳米平台，来协调热疗/ROS抗生物膜疗法、毒素中和和免疫调节疗法。在生物膜微环境中，成孔毒素会主动攻击纳米点上的红细胞膜并被截留，从而远离其靶标并减轻组织损伤。在近红外（NIR）激光照射下，具有出色光热和类过氧化物酶（POD）特性的二硫化钼纳米点发挥强大的协同抗生物膜作用。更有趣的是，我们首次发现它们具有通过将巨噬细胞从抗炎表型转变为促炎表型来逆转免疫抑制微环境的能力，这将促进生物膜碎片的清除并防止感染复发。系统的研究和评估表明，EM@MoS具有显著的抗生物膜效果。当前的研究整合了热疗/ROS疗法、毒力清除和免疫调节的功能，可为IRI治疗提供一种有效的范例。
