Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford University, 3155 Porter Drive, Palo Alto, California 94305, United States.
Infectious Disease Division, Department of Medicine, Rhode Island Hospital and Alpert Medical School of Brown University, Brown University, Providence, Rhode Island 02903, United States.
ACS Nano. 2020 May 26;14(5):5818-5835. doi: 10.1021/acsnano.0c00921. Epub 2020 May 4.
() is a highly pathogenic facultative anaerobe that in some instances resides as an intracellular bacterium within macrophages and cancer cells. This pathogen can establish secondary infection foci, resulting in recurrent systemic infections that are difficult to treat using systemic antibiotics. Here, we use reconstructed apoptotic bodies (ReApoBds) derived from cancer cells as "nano decoys" to deliver vancomycin intracellularly to kill by targeting inherent "eat me" signaling of ApoBds. We prepared ReApoBds from different cancer cells (SKBR3, MDA-MB-231, HepG2, U87-MG, and LN229) and used them for vancomycin delivery. Physicochemical characterization showed ReApoBds size ranges from 80 to 150 nm and vancomycin encapsulation efficiency of 60 ± 2.56%. We demonstrate that the loaded vancomycin was able to kill intracellular efficiently in an model of infected RAW-264.7 macrophage cells, and U87-MG (p53-wt) and LN229 (p53-mt) cancer cells, compared to free-vancomycin treatment ( < 0.001). The vancomycin loaded ReApoBds treatment in infected macrophages showed a two-log-order higher CFU reduction than the free-vancomycin treatment group. studies revealed that ReApoBds can specifically target macrophages and cancer cells. Vancomycin loaded ReApoBds have the potential to kill intracellular infection in macrophages and cancer cells.
()是一种高致病性兼性厌氧菌,在某些情况下,它作为一种细胞内细菌存在于巨噬细胞和癌细胞中。这种病原体可以建立继发性感染病灶,导致复发性全身感染,使用全身抗生素难以治疗。在这里,我们使用源自癌细胞的重建凋亡体(ReApoBds)作为“纳米诱饵”,通过靶向 ApoBds 的固有“吃我”信号将万古霉素递送到细胞内杀死 。我们从不同的癌细胞(SKBR3、MDA-MB-231、HepG2、U87-MG 和 LN229)中制备 ReApoBds,并将其用于万古霉素的递送。物理化学特性表明 ReApoBds 的大小范围为 80 至 150nm,万古霉素包封效率为 60±2.56%。我们证明,负载的万古霉素能够在感染 RAW-264.7 巨噬细胞的 模型中有效杀死细胞内的 ,与游离万古霉素治疗相比(<0.001)。与游离万古霉素治疗组相比,感染巨噬细胞中负载万古霉素的 ReApoBds 治疗可使 CFU 减少两对数。研究表明,ReApoBds 可以特异性靶向巨噬细胞和癌细胞。负载万古霉素的 ReApoBds 有可能杀死巨噬细胞和癌细胞中的细胞内 感染 。