文献：Resveratrol-modified mesoporous silica nanoparticle for tumor-targeted therapy of gastric cancer

文献链接：https://pubmed.ncbi.nlm.nih.gov/34506231/

作者：Mingzhen Lin, Wenxia Yao, Yao Xiao, Zhijie Dong, Wei Huang, Fan Zhang, Xinke Zhou & Min Liang

相关产品：单分散二氧化硅

原文摘要：Resveratrol (Res) has been shown to exhibit anti-cancer properties in gastric cancer. However, its clinical application is limited by its poor pharmacokinetics, stability, and low solubility. Hence, this study aimed to explore and verify a better delivery system for gastric cancer therapy. Using transmission electron microscopy, Fourier transform infrared (FTIR) spectroscopy, and ultraviolet (UV) spectrometry, we observed the shape and encapsulation of resveratrol-modified mesoporous silica nanoparticles (MSN-Res) that were synthesized by chemical methods. To explore the anticancer effects of these MSN-Res in vivo and in vitro, we established AGS and HGC-27 tumorbearing mouse models. Meanwhile, the proliferation of gastric cancer cells in vitro and in vivo was assessed by Cell Counting Kit-8, EdU, and Ki-67 immunohistochemical staining methods, while cellular apoptosis, and invasion and migration were detected by TdT-mediated dUTP nick end labeling (TUNEL) and Transwell assays, respectively. FTIR and UV results showed that we successfully synthesized and loaded drugs. Safety evaluation experiments showed that neither MSN-SH nor MSN-Res had toxic effects on the normal tissues of animals. Moreover, in vitro experiments revealed that MSN-Res significantly inhibited the proliferation, invasion, and migration of gastric cancer cells. Furthermore, TUNEL assay showed that MSN-Res promoted apoptosis in gastric cancer. These results were confirmed by the nude mouse tumorigenesis experiment. In conclusion, we demonstrated that MSN-Res showed better inhibitory effect on the development of gastric cancer than Res alone, indicating that MSN-Res could be a promising drug delivery system for gastric cancer treatment.

白藜芦醇（Res）具有抗cancer作用。但由于其药代动力学差、稳定性差和溶解度低，因此，探索和验证一种较好的胃cancer给药系统。利用透射电子显微镜、傅里叶变换红外（FTIR）光谱和紫外（UV）光谱，观察了化学方法合成的白藜芦醇修饰介孔二氧化硅纳米颗粒（MSN-Res）的形状和封装情况。MSN-SH和MSN-Res对动物的正常组织均无害。此外，MSN-Res可抑制胃cancer细胞的增殖、侵袭和迁移。TUNEL检测结果显示，MSN-Res可促进胃cancer细胞Apoptosis 。

单分散二氧化硅，依次用官能基团-SH和-SHCOOH进行修饰，然后将Res加载到修饰后的单分散二氧化硅表面，用PEI-FA按照方法进行修饰。将十六烷基三甲基溴化铵（CTAB）和氢氧化钠加入到去离子水中，然后加热。然后，在溶液中缓慢加入正硅酸四乙酯、3-巯基丙基三甲氧基硅烷（MPTMS）保存。将得到的MSN-SH用蒸馏水和乙醇洗涤，真空干燥，然后，通过允许MSN-SH与Py-SSPy、二甲基甲酰胺（DMF）、 3-巯基丙酸和乙酸反应得到MSN-SHCOOH。超声将改性MSN-SHCOOH重悬于含res无水乙醇中，在黑暗中搅拌，装载res的单分散二氧化硅离心后用乙醇和水洗涤。将RES的MSN与PEI-FA偶联，得到MSN/Res-PEI-FA。

利用透射电镜（TEM）观察了res修饰的单分散二氧化硅的亚定位。装载res的单分散二纳米硅用戊二醛溶液固定，然后用预冷磷酸盐缓冲盐水冲洗。然后，用的四氧化锇和碳酸钙缓冲液将细胞后固定，然后在室温下干燥。傅里叶变换红外（FTIR）光谱法，确定了不同官能团和Res的二分散二氧化硅的掺入和吸收峰。

图：（FTIR）光谱法检测不同表面改性的单分散二氧化硅的振动峰

结论：单分散二氧化硅具有高载药能力、良好的生物相容性和易于表面修饰。它们也有可调节的孔径，这允许控制药物释放。研究成功地制备了res修饰的单分散二氧化硅，并对其特性进行了表征。功能分析表明，Res修饰的单分散二氧化硅Treatment 胃cancer的抗tumor作用优于单独修饰的Res，并成功实现了Res满载功能化单分散二纳米硅，吸附在细胞表面而不破坏细胞膜或细胞形态，具有较高的生物安全性。