文献：A hybrid membrane coating nanodrug system against gastric cancer via the VEGFR2/STAT3 signaling pathway

文献链接：https://d.wanfangdata.com.cn/periodical/a1dd931fc9dfff14386aa56c927df119

作者：Ying Long, Zhou Wang, Jialong Fan, Liqin Yuan,Chunyi Tong, Yanzhong Zhaoand Bin Liu

相关产品：DSPE-PEOz2K（磷脂-聚（2 -乙基- 2-噁唑啉）2K）

原文摘要：

Although drug combination has proved to be an efficient strategy for clinic gastric cancer therapy, how to further improve their bioavailability and reduce the side effects are still challenges due to the low solubility and untargeted ability of drugs. Recently, newly emerging nanotechnology has provided an alternative for constructing new drug delivery systems with high targeting ability and solubility. In this study, a pH-responsive liposome (Liposome-PEO, LP) loaded with apatinib (AP) and cinobufagin (CS-1) was used for combinational therapy against gastric cancer after coating with a hybrid membrane (R/C). The results indicated that the constructed nanocomplex LP-R/C@AC not only efficiently killed tumor cells in vitro by inducing apoptosis, autophagy, and pyroptosis, but also significantly inhibited tumor invasion and metastasis via the VEGFR2/STAT3 pathway. Moreover, it showed stronger anti-tumor activity in gastric cancer-bearing mouse models, as compared to the sole drugs. A naturally-derived hybrid cell membrane coating bestowed nanocomplexes with enhanced biointerfacing including prolonged circulation time and targeting ability.

DSPE 代表 1,2 -二硬脂酰- sn -甘油- 3 -磷酸乙醇胺，是一种磷脂。它有亲水性的头部（磷酸乙醇胺部分）和两条疏水性的长链脂肪酸（硬脂酸）部分。PEOz 是聚（2 -乙基- 2 -噁唑啉），DSPE - PEOz2K 中的 “2K” 表示聚（2 -乙基- 2-噁唑啉）部分的分子量约为 2000Da。它同样具有两亲性结构。DSPE 部分的疏水性长链脂肪酸能够与疏水性物质相互作用，而 PEOz 部分则具有亲水性。这种两亲性使其在水溶液中能够自组装形成一些特殊的结构，如胶束或者囊泡等。其结构特点与传统的 PEG（聚乙二醇）修饰的磷脂类似，但是 PEOz 具有一些特殊的物理化学性质，比如更好的生物相容性和更低的蛋白吸附性等优点。ph敏感的脂质DSPE-PEOz也能加速酸性环境下化合物的释放。该文献基于DSPE - PEOz2K的性质，合成的新型材料LP-R/C@AC NPs流程如下：

图：产品制备方案

利用DSPE-PEOz2K制备LP-R/C@AC NPs：

将卵磷脂、胆固醇、DSPE-PEOz、AP和CS-1溶解在氯仿中。超声处理后，转移到圆底瓶中，在低压下蒸发氯仿。用PBS水合，旋转乳化。脂质体-peo-AP-CS-1（LP@AC）产品超声，然后通过不同孔径过滤器的脂质体手动挤出器进行超声处理。然后，将LP@AC与杂交膜（R/C）混合，搅拌。混合物通过手动挤压机挤出，得到的均匀的LP-R/C@AC NPs用于后续实验。

图：对照组

结论：

该文献成功制备出了基于DSPE-PEOz2K修饰的LP-R/C@AC NPs，实验结果表明，构建的纳米复合物LP-R/C@AC不仅通过诱导细胞Apoptosis 、自噬和焦亡有效kill tumour细胞，而且通过VEGFR2/STAT3通路明显控制tumour的侵袭转移。这种天然衍生的混合细胞膜涂层赋予了增强生物界面的纳米复合物，包括延长循环时间和靶向能力。