Shanghai Institute of Ceramics, Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai 200050, P. R. China.
Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
Sci Adv. 2024 Nov;10(44):eadp3976. doi: 10.1126/sciadv.adp3976. Epub 2024 Oct 30.
In the competition between the pathogen infection and the host defense, infectious microorganisms may enter the host cells by evading host defense mechanisms and use the intracellular biomolecules as replication nutrient. Among them, intracellular relies on the host cells to protect itself from the attacks by antibiotics or immune system to achieve long-term colonization in the host, and the consequent clinical therapeutic failures and relapses after antibiotic treatment. Here, we demonstrate that intracellular surviving well even in the presence of vancomycin can be effectively eliminated using an emerging cell-mimicking therapeutic strategy. These cell mimics with natural killer cell-like activity (NKMs) are composed of a redox-responsive degradable carrier, and perforin and granzyme B within the carrier. NKMs perform far more effectivly than clinical antibiotics in treating intracellular bacterial infections, providing a direct evidence of the NK cell-mimicking immune mechanism in the treatment of intracellular .
在病原体感染和宿主防御的竞争中,感染性微生物可能通过逃避宿主防御机制进入宿主细胞,并利用细胞内生物分子作为复制营养物质。其中,细胞内细菌依赖宿主细胞来保护自己免受抗生素或免疫系统的攻击,从而在宿主中长期定植,导致临床治疗失败和抗生素治疗后的复发。在这里,我们证明,即使在万古霉素存在的情况下,能够很好地存活的细胞内细菌也可以通过一种新兴的细胞模拟治疗策略有效地消除。这些具有自然杀伤细胞样活性 (NKMs) 的细胞模拟物由一个氧化还原响应性可降解载体,以及载体内部的穿孔素和颗粒酶 B 组成。NKMs 在治疗细胞内细菌感染方面比临床抗生素更有效,为 NK 细胞模拟免疫机制在治疗细胞内细菌中的作用提供了直接证据。