Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, People's Republic of China.
Department of Central Laboratory, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, People's Republic of China.
Int J Nanomedicine. 2020 Apr 23;15:2873-2884. doi: 10.2147/IJN.S242787. eCollection 2020.
The primary goal of the present study was to design doxorubicin (DOX)-loaded superparamagnetic iron oxide (SPIO) nanoparticles (NPs) coated with mesenchymal stem cell (MSC) membranes and explore their effect on colon cancer in vitro and in vivo.
DOX-SPIO NPs were coated with MSC membranes using an extruder, and the morphological characteristics of MSC membrane-camouflaged nanodrug (DOX-SPIO@MSCs) evaluated by transmission electron microscopy (TEM) and NP-tracking analysis. Drug loading and pH response were assessed by UV spectrophotometry. Intracellular colocalization was analyzed using NP-treated MC38 cells stained with 3,3'-dioctadecyloxacarbocyanine perchlorate and Hoechst 33342. Cellular uptake was analyzed using an inverted fluorescence microscope and flow cytometry and cytotoxicity evaluated by cell counting kit-8 assay. Biological compatibility was assessed by hemolysis analysis, immunoactivation test and leukocyte uptake experiments. Furthermore, intravenous injection of chemotherapy drugs into MC38 tumor-bearing C57BL/6 mice was used to study anti-tumor effects.
Typical core-shell NP structures were observed by TEM. Particle size remained stable in fetal bovine serum and phosphate-buffered saline (PBS). Compared with DOX-SPIO, DOX-SPIO@MSCs improved cellular uptake efficiency, enhanced anti-tumor effects, and reduced the immune system response. Animal experiments demonstrated that DOX-SPIO@MSCs enhanced tumor treatment efficacy while reducing systemic side effects.
Our experimental results demonstrate that DOX-SPIO@MSCs are a promising targeted nanocarrier for application in treatment of colon cancer.
本研究的主要目的是设计载多柔比星（DOX）的超顺磁性氧化铁（SPIO）纳米粒子（NPs），并将其包裹在间充质干细胞（MSC）膜中，探讨其在体外和体内对结肠癌的作用。
采用挤出机将 DOX-SPIO NPs 包裹在 MSC 膜中，通过透射电子显微镜（TEM）和 NP 跟踪分析评估 MSC 膜伪装纳米药物（DOX-SPIO@MSCs）的形态特征。通过紫外分光光度法评估药物负载和 pH 响应。通过用 3,3'-二辛氧羰氰基过氯酸和 Hoechst 33342 染色 NP 处理的 MC38 细胞分析细胞内共定位。使用倒置荧光显微镜和流式细胞术分析细胞摄取，并通过细胞计数试剂盒-8 测定法评估细胞毒性。通过溶血分析、免疫激活试验和白细胞摄取实验评估生物相容性。此外，通过静脉注射化疗药物到 MC38 荷瘤 C57BL/6 小鼠来研究抗肿瘤作用。
TEM 观察到典型的核壳 NP 结构。在胎牛血清和磷酸盐缓冲盐水（PBS）中，粒径保持稳定。与 DOX-SPIO 相比，DOX-SPIO@MSCs 提高了细胞摄取效率，增强了抗肿瘤效果，降低了免疫系统反应。动物实验表明，DOX-SPIO@MSCs 增强了肿瘤治疗效果，同时减少了全身副作用。
我们的实验结果表明，DOX-SPIO@MSCs 是一种有前途的靶向纳米载体，可用于治疗结肠癌。
