Staphylococcus Aureus Membrane Vesicles Kill Tumor Cells Through a Caspase-1-Dependent Pyroptosis Pathway

作者：Mengyang Li, Yuting Wang, He Liu, Xiaonan Huang, Huagang Peng, Yi Yang, Zhen Hu, Jianxiong Dou, Chuan Xiao, Juan Chen, Weilong Shang, Xiancai Rao · 发表于：International Journal of Nanomedicine · 年份：2024 · DOI：10.2147/ijn.s455158 · 被引用次数：14 · 研究领域：Inflammasome and immune disorders、Bacterial Infections and Vaccines、ATP Synthase and ATPases Research

Introduction: Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated. Methods: MVs of Staphylococcus aureu s USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2–MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor. Results: The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 μg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2–MVs (R 2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10 − 3 μg. Antares2–MVs can directly target tumor tissues in vivo, and 20 μg/mL Antares2–MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD...