State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China.
National Engineering Research Center of Ultrasound Medicine, Chongqing, 401121, China.
J Mol Histol. 2024 Nov 27;56(1):5. doi: 10.1007/s10735-024-10296-0.
To seek out the targeting of Escherichia coli outer membrane vesicles (E. coli OMVs) in breast tumor-bearing mice and their biosafety in healthy mice. Ultrafiltration in conjunction with ultracentrifugation was utilized to concentrate E. coli OMVs, and characterize them. Subcutaneous breast tumors were induced in BALB/c mice to serve as an experimental model, and the biodistribution of E. coli OMVs in both tumor-bearing and healthy mice was monitored using an in vivo fluorescence imaging system. Utilizing frozen sections, the infiltration of E. coli OMVs in tumor tissues was appraised at the 24-hour post-injection. Healthy BALB/c mice were randomly divided into control group and vesicles group. Following the intravenous injection of E. coli OMVs, monitoring encompassed variations in body weight, blood routine indices, serum levels of AST, ALT, and BUN, organ indices (heart, liver, spleen, lung, and kidney), along with tissue histopathology over a 14-day period. The spherical E. coli OMVs had a diameter of (155.8 ± 3.1) nm and exhibited the expression of outer membrane proteins OmpA and OmpC. Upon assessment, it was evident that the E. coli OMVs persisted in the tumor tissues even 24 h post-injection. An evident decrease in the body weight of the vesicles group, distinct from the control group, was observed on the second day after injection (P < 0.001); in contrast, no considerable differences were noted at subsequent time points (P > 0.05). Following the injection, the vesicles group displayed notable reductions in WBC and PLT as relative to the control group (P < 0.0001) on the initial day, however, there were no noteworthy distinctions as opposed to the control group for other hematological indices; No notable variances in hematological indices between the two groups were observed on the seventh and fourteenth day (P > 0.05). Over the 14 days, no substantial differences were observed in the serum levels of BUN, AST, ALT, and organ indices within the vesicles group as opposed to the control group (P > 0.05). Furthermore, there were no obvious abnormal changes in tissue morphology. 0.5 mg/kg of E. coli OMVs can safely and effectively target 4T1 breast tumor in mice.
为了寻找大肠杆菌外膜囊泡（E. coli OMVs）在乳腺癌荷瘤小鼠中的靶向性及其在健康小鼠中的生物安全性。采用超滤与超速离心联合法浓缩大肠杆菌 OMVs，并对其进行表征。在 BALB/c 小鼠中诱导皮下乳腺癌作为实验模型，并用体内荧光成像系统监测 E. coli OMVs 在荷瘤和健康小鼠中的分布情况。利用冰冻切片评估 E. coli OMVs 在肿瘤组织中的渗透情况，注射后 24 小时。将健康 BALB/c 小鼠随机分为对照组和囊泡组。静脉注射 E. coli OMVs 后，连续 14 天监测体重变化、血常规指标、血清 AST、ALT 和 BUN 水平、器官指数（心、肝、脾、肺、肾）及组织病理学变化。大肠杆菌 OMVs 呈球形，直径为（155.8±3.1）nm，表达外膜蛋白 OmpA 和 OmpC。评估结果显示，即使在注射后 24 小时，大肠杆菌 OMVs 仍存在于肿瘤组织中。与对照组相比，囊泡组在注射后第二天体重明显下降（P<0.001）；但在随后的时间点，差异无统计学意义（P>0.05）。与对照组相比，囊泡组在注射后第一天白细胞（WBC）和血小板（PLT）明显减少（P<0.0001），但其他血液学指标与对照组无显著差异；两组在第 7 天和第 14 天的血液学指标无显著差异（P>0.05）。在 14 天内，囊泡组与对照组相比，血清 BUN、AST、ALT 水平和器官指数均无显著差异（P>0.05）。此外，组织形态学无明显异常变化。0.5mg/kg 的大肠杆菌 OMVs 可安全有效地靶向小鼠 4T1 乳腺癌。
