Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
Daru. 2020 Jun;28(1):171-180. doi: 10.1007/s40199-020-00328-x. Epub 2020 Jan 31.
Rod-like mesoporous silica nanoparticles with pH-responsive amphiphilic hyperbranched polyester shells were prepared for doxorubicin (DOX) delivery. First, rod-shaped mesoporous silica nanoparticles (MSNs) were obtained, then hydrophobic hyperbranched polyester Boltorn H40 (H40) was grafted on their surface. The H40 coated MSNs were next treated with amine-functionalized polyethylene glycol (PEG) to achieve the hydrophilic and pH-responsive material denoted as PEG-H40-MSNs. The experimental results showed that PEG-H40-MSNs were successfully synthesized. BET analysis showed that rod MSNs exhibits a type IV standard isotherm. TEM revealed that the thin gray polymer layer was formed around the SBA-15 particle with a diameter of around 150 nm. DOX was effectively loaded, which can be released according to the ambient pH inside the cell as follow: at pH 7.4, only 9.7% of the DOX was released after 48 h; as the pH decreased to 5.5, the cumulative release reached to 49% at the same time. PEG-H40-MSNs showed less than 1.6% of hemolytic activity and a slight effect on the liver and kidney of treated mice were observed at a high disposal dosage implying negligible toxicities were caused by PEG-H40-MSNs in both in vitro hemolysis analysis and in vivo biochemical in mice. However, the in vitro cytotoxicity evaluation of the DOX-PEG-H40-MSNs showed that the cell cytotoxicity of both pure DOX and DOX-loaded PEG-H40-MSNs generally enhanced by increasing the concentration of DOX. Graphical abstract Schematic of cellular uptake and DOX release of PEG-H40-MSNs nanoparticle.
具有 pH 响应性两亲超支化聚酯壳的棒状介孔硅纳米粒子被制备用于阿霉素（DOX）递送。首先，获得棒状介孔硅纳米粒子（MSNs），然后将疏水性超支化聚酯 Boltorn H40（H40）接枝到其表面。接下来，用胺功能化的聚乙二醇（PEG）处理 H40 涂层的 MSNs，以获得亲水性和 pH 响应性材料，称为 PEG-H40-MSNs。实验结果表明，成功合成了 PEG-H40-MSNs。BET 分析表明，棒状 MSNs 表现出 IV 型标准等温线。TEM 显示，直径约为 150nm 的 SBA-15 颗粒周围形成了一层薄的灰色聚合物层。DOX 被有效负载，其可以根据细胞内的环境 pH 释放，如下所示：在 pH 7.4 时，48h 后仅释放了 9.7%的 DOX；当 pH 降低至 5.5 时，同一时间累积释放达到 49%。PEG-H40-MSNs 的溶血活性小于 1.6%，并且在高处理剂量下观察到对处理小鼠的肝和肾的影响很小，这表明 PEG-H40-MSNs 在体外溶血分析和体内生化分析中均不会引起明显的毒性。然而，DOX-PEG-H40-MSNs 的体外细胞毒性评估表明，纯 DOX 和负载 DOX 的 PEG-H40-MSNs 的细胞毒性通常随着 DOX 浓度的增加而增强。
