School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou, 450046, China.
China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
J Nanobiotechnology. 2023 Dec 20;21(1):492. doi: 10.1186/s12951-023-02267-6.
Effective diagnosis and therapy for bacterial infections, especially those caused by multidrug-resistant (MDR) species, greatly challenge current antimicrobial stewardship. Monocytes, which can chemotactically migrate from the blood to infection site and elicit a robust infection infiltration, provide a golden opportunity for bacterial theranostics. Here, a nano-Trojan Horse was facilely engineered using mannose-functionalized manganese-eumelanin coordination nanoparticles (denoted as MP-MENP) for precise two-step localization and potent photothermal-immunotherapy of MDR bacterial infection. Taking advantage of the selective recognition between mannose and inflammation-associated monocytes, the MP-MENP could be passively piggybacked to infection site by circulating monocytes, and also actively target infiltrated monocytes that are already accumulated in infection microenvironment. Such dual-pronged targeting enabled an efficient imaging diagnosis of bacterial infection. Upon laser irradiation, the MP-MENP robustly produced local hyperemia to ablate bacteria, both extracellularly and intracellularly. Further combined with photothermal therapy-induced immunogenic cell death and MP-MENP-mediated macrophage reprogramming, the immunosuppressive infection microenvironment was significantly relieved, allowing an enhanced antibacterial immunity. Collectively, the proposed nanotheranostic Trojan Horse, which integrates dual-pronged targeting, precise imaging diagnosis, and high-performance photothermal immunotherapy, promises a new way for complete eradication of MDR bacterial infection.
有效诊断和治疗细菌感染，尤其是由多药耐药（MDR）物种引起的感染，对当前的抗菌药物管理提出了巨大挑战。单核细胞可以趋化性地从血液迁移到感染部位，并引发强烈的感染浸润，为细菌治疗提供了一个绝佳的机会。在这里，使用甘露糖功能化的锰-真黑素配位纳米颗粒（表示为 MP-MENP），通过两步精确定位和强大的光热免疫治疗，简便地构建了一个纳米“木马”，用于治疗 MDR 细菌感染。利用甘露糖与炎症相关的单核细胞之间的选择性识别，MP-MENP 可以被循环单核细胞被动地携带到感染部位，也可以主动靶向已经在感染微环境中积累的浸润单核细胞。这种双管齐下的靶向作用使细菌感染的成像诊断变得高效。激光照射后，MP-MENP 会产生强烈的局部充血，以消灭细胞外和细胞内的细菌。此外，结合光热治疗诱导的免疫原性细胞死亡和 MP-MENP 介导的巨噬细胞重编程，显著缓解了免疫抑制性感染微环境，增强了抗菌免疫。总之，所提出的纳米治疗性“木马”结合了双靶向、精确的成像诊断和高性能的光热免疫治疗，为彻底消除 MDR 细菌感染提供了一种新方法。
