目的

通过已制备的PH 超敏感聚合物纳米囊共溶体DOX 和Navitoclax，研究其在子宫内膜癌的体内体外抗癌作用，并评价其安全性。

方法

体外培养人子宫内膜腺癌细胞系Ishikawa，建立Ishikawa 细胞系体内移植瘤动物模型；注射DIR 标记的纳米囊（已构建纳米囊共溶体），记录体内荧光图像；荷瘤小鼠分为PBS、NP@DOX、NP@Nav 以及NP@DOX/Nav 治疗组共四组，检测和记录小鼠的肿瘤体积、体重以及死亡率，以评价药物体内抗癌功效；收集各治疗组小鼠器官进行组织学和免疫组织化学检测，使用TUNEL 检测试剂盒进行原位细胞死亡分析；采集各治疗组血清测定ALT、TBIL、BUN 和Cr 水平，评估各治疗组治疗后的病理和生化变化。

结果

体内荧光成像研究显示肿瘤部位的荧光信号强度在注射后仍保持高达36 h 的高水平；NP@Nav/DOX 治疗组对小鼠移植瘤模型产生最佳抗瘤效果；TUNEL 分析显示NP@Nav/DOX 组表现出最高水平的癌细胞凋亡；检测血清中ALT、BUN、TBIL 和Cr 的生化指标在不同处理后无明显变化，证实了纳米囊的体内低毒性。

结论

已成功制备的PH 超敏感聚合物纳米囊共溶体DOX 和Navitoclax，在子宫内膜癌中具有良好的协同抗癌作用，具有广阔的临床应用前景。

Objective

To investigate the anti-cancer effects of ultra-PH-sensitive polymeric nanovesicle-mediated co-delivery of doxorubicin (DOX) and Navitoclax (Nav) in vivo and in vitro, and to evaluate their safety.

Methods

The human endometrial adenocarcinoma cell line Ishikawa was cultured in vitro, and an in vivo tumor model was established by transplanting Ishikawa cells into mice. Fluorescent images were recorded by injecting DIR-labeled nanovesicles (constructed nanocapsicles for co-delivery of DOX and Nav) into the mice. Mice bearing tumors were divided into four groups: PBS, NP@DOX, NP@Nav,and NP@DOX/Nav treatment groups, and tumor volume, body weight, and mortality rate were monitored and recorded to evaluate the anti-cancer efficacy of the drugs in vivo. The organs of mice in each treatment group were collected for histological and immunohistochemical examination, and TUNEL assay was used for in situ cell death analysis. Serum levels of ALT, TBIL, BUN, and Cr were measured in each group to evaluate the pathological and biochemical changes after treatment.

Results

The fluorescent signal intensity at the tumor site remained high for up to 36 hours after injection. The NP@Nav/DOX treatment group produced the best anti-tumor effect in the mouse xenograft model. TUNEL analysis showed that the NP@Nav/DOX group exhibited the highest level of cancer cell apoptosis. The biochemical indicators of ALT, BUN, TBIL, and Cr in the serum were not significantly changed after different treatments, confirming the low toxicity of the nanovesicles in vivo.

Conclusion

The ultra-PH-sensitive polymeric nanovesicles for co-delivery of DOX and Nav have been successfully prepared, demonstrating a good synergistic anticancer effect of DOX and Nav in endometrial carcinoma.