Evodiamine (EVO) and Berberine (BBR), from Euodiae Fructus and Coptidis rhizoma, have been used as an herbal medicine pair in traditional Chinese medicine to exert synergistic antitumor effects against various types of tumor cells. However, their clinical use is limited by their poor solubility and adverse toxic side effects. Mesoporous silica nanoparticles (MSNs) possess excellent properties such as a readily functionalized surface, prominent biocompatibility, and huge specific surface area for loading with hydrophobic and hydrophilic drug. On this basis, a novel temperature- and pH-responsive dual drug delivery platform has been developed, in which lipid-coated [email protected](NIPAM-co-MA) codelivers EVO and BBR. The results indicate that the nanocarrier improves the efficacy and biocompatibility of the drug pair and maintain desirable drug profiles at the low pH and higher temperature of the tumor microenvironment. The dual drug-loaded MSNs showed excellent synergistic therapy effects in vitro (cytotoxicity, cell migration and invasion, angiogenesis) and in vivo (growth of tumor grafts in mice). Meanwhile, the dual drug-loaded nanoparticles showed lower systemic toxicity than either drug alone, the free drug combination, or Taxol. These results suggest that the temperature- and pH-sensitive lipid-coated MSNs are a promising novel carrier for both hydrophobic and hydrophilic drugs.

中文翻译：

---

基于热和pH值的脂质包裹的介孔二氧化硅纳米颗粒双重药物递送系统，可提高疏水性药物的抗肿瘤作用

来自中药Euodiae Fructus和Coptidis rhizoma的Evodiamine（EVO）和Berberine（BBR）已被用作传统中药中的草药，可对多种类型的肿瘤细胞发挥协同抗肿瘤作用。但是，它们的不良溶解性和不良的毒副作用限制了它们的临床应用。介孔二氧化硅纳米粒子（MSN）具有优异的性能，例如易于官能化的表面，突出的生物相容性和巨大的比表面积，可装载疏水性和亲水性药物。在此基础上，开发了一种新型的温度和pH响应双重药物递送平台，其中脂质包裹的[电子邮件保护]（NIPAM- co-MA）代码提供EVO和BBR。结果表明，纳米载体改善了药物对的功效和生物相容性，并在肿瘤微环境的低pH和较高温度下保持了理想的药物分布。载有双重药物的MSN在体外（细胞毒性，细胞迁移和侵袭，血管生成）和体内（小鼠肿瘤移植物的生长）显示出优异的协同治疗效果。同时，载有双重药物的纳米颗粒显示出比单独药物，游离药物组合或紫杉醇更低的全身毒性。这些结果表明，对温度和pH敏感的脂质包覆的MSN是疏水和亲水药物的一种有希望的新型载体。