Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Ji'nan, Shandong, People's Republic of China.
Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Ji'nan, Shandong, People's Republic of China.
Acta Biomater. 2017 Nov;63:150-162. doi: 10.1016/j.actbio.2017.08.050. Epub 2017 Sep 2.
A novel and intelligent pH-controlled system having an "on-off" switch based on poly(l-histidine) (PLH) and poly(ethylene glycol) (PEG) coated mesoporous silica nanoparticles (MSNs) (MSNs-PLH-PEG) was designed and evaluated for tumor specific drug release. The unsaturated nitrogen-rich polymer, PLH, which can change its solubility at different pH values, was employed for establishing the reversible "on-off" switch. In vitro drug release results demonstrated that MSNs-PLH-PEG has a pH-controlled "on-off" profile with the change of pH value between pH 7.4 and 5.0. Furthermore, in vitro cellular uptake study results showed that the entrapped drug could be efficiently released from MSNs-PLH-PEG under acidic endosome/lysosome. In vitro cell cytotoxicity and in vivo antitumor studies results indicated that sorafenib loaded MSNs-PLH-PEG exhibited good anti-proliferation and tumor growth inhibition effects. Haemolysis assay and histological analysis of MSNs-PLH-PEG showed negligible haemolysis activity and no visible tissue toxicity at the test dose. This study represents a promising and intelligent pH-controlled intelligent system for drug delivery and controlled release.
A novel pH-controlled intelligent and reversible "on-off" switch system based on poly(l-histidine) and poly(ethylene glycol) coated mesoporous silica nanoparticles (MSNs-PLH-PEG) by "graft to" synthesis method was constructed for tumor specific drug release. The unsaturated nitrogen-rich pH-sensitive polymer, PLH, which can change its solubility in different pH values, was employed as the reversible "on-off" switch in MSNs for the first time. The pH-controlled "on-off" switch manner was observed in the drug release results in vitro. In the in vivo antitumor studies, sorafenib loaded MSNs-PLH-PEG could effectively suppressed tumor growth in H22 tumor bearing mice. It is expected that the pH-controlled intelligent "on-off" switch system we designed holds remarkable promise and provides valuable strategy for possible applications in cancer therapy.
设计并评价了一种基于聚（L-组氨酸）（PLH）和聚乙二醇（PEG）包覆介孔硅纳米粒子（MSNs）（MSNs-PLH-PEG）的新型智能 pH 控制体系作为肿瘤特异性药物释放的“开-关”开关。可以在不同 pH 值下改变其溶解度的不饱和富氮聚合物 PLH 被用于建立可逆的“开-关”开关。体外药物释放结果表明，MSNs-PLH-PEG 在 pH 值为 7.4 和 5.0 之间变化时具有 pH 控制的“开-关”特性。此外，体外细胞摄取研究结果表明，在酸性内涵体/溶酶体中，包封的药物可以从 MSNs-PLH-PEG 中有效释放。体外细胞毒性和体内抗肿瘤研究结果表明，索拉非尼负载的 MSNs-PLH-PEG 表现出良好的抗增殖和肿瘤生长抑制作用。MSNs-PLH-PEG 的溶血试验和组织学分析表明，在测试剂量下，溶血活性可忽略不计，无明显组织毒性。该研究代表了一种有前途的智能 pH 控制智能药物输送和控制释放系统。
通过“接枝到”合成方法构建了基于聚（L-组氨酸）和聚乙二醇包覆介孔硅纳米粒子（MSNs-PLH-PEG）的新型 pH 控制智能和可逆“开-关”开关系统，用于肿瘤特异性药物释放。首次将可改变不同 pH 值下溶解度的不饱和富氮 pH 敏感聚合物 PLH 用作 MSNs 中的可逆“开-关”开关。在体外药物释放研究中观察到 pH 控制的“开-关”开关方式。在体内抗肿瘤研究中，索拉非尼负载的 MSNs-PLH-PEG 可有效抑制 H22 荷瘤小鼠的肿瘤生长。预计我们设计的 pH 控制智能“开-关”开关系统具有显著的应用前景，并为癌症治疗的可能应用提供了有价值的策略。
