Unsaturated nitrogen-rich polymer poly(L-histidine) gated reversibly switchable mesoporous silica nanoparticles using "graft to" strategy for drug controlled release
Unsaturated nitrogen-rich polymer poly(L-histidine) gated reversibly switchable mesoporous silica nanoparticles using "graft to" strategy for drug controlled release
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不饱和富氮聚合物聚（L-组氨酸）门控可逆可逆介孔二氧化硅纳米颗粒，采用“接枝”策略实现药物控制释放
DOI：
10.1016/j.actbio.2017.08.050
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发表时间：
2017-11-01
影响因子：
9.7
通讯作者：
Zhang, Na
中科院分区：
文献类型：
--
作者：
Mu, Shengjun;Liu, Yongjun;Zhang, Na
设计了一种基于聚t-组氨酸（PLH）和聚乙二醇（PEG）包覆的介孔二氧化硅纳米粒子（MSNs）（MSNs-PLH-PEG）的具有“开关”的新型智能pH控制系统，并对该系统的肿瘤特异性药物释放进行了评价。利用不饱和富氮聚合物PLH在不同pH值下的溶解度变化，建立了可逆的“开关”。体外药物释放结果表明，随着pH值在pH7.4和5.0之间变化，MSNs-PLH-PEG具有pH控制的“开关”曲线。体外细胞摄取实验结果表明，在酸性内体/溶酶体条件下，包埋药物可从MSNs-PLH-PEG中有效释放。体外细胞毒性和体内抗肿瘤实验结果表明，索拉非尼负载的MSNs-PLH-PEG具有良好的抗增殖和抑制肿瘤生长的作用。MSNs-PLH-PEG的溶血测定和组织学分析显示在测试剂量下可忽略的溶血活性和无可见的组织毒性。本研究以聚组氨酸和聚乙二醇包覆介孔二氧化硅纳米粒子（MSNs-PLH-PEG），通过“接枝”合成方法，构建了一种新型的pH可控的、可逆的、智能的“开关”系统，用于肿瘤特异性药物释放。不饱和富氮pH敏感聚合物PLH在不同pH值下的溶解度会发生变化，首次将其用作微纳传感器的可逆开关。体外释药实验结果表明，微球的释药过程中存在pH控制的“开关”现象。在体内抗肿瘤研究中，索拉非尼负载的MSNs-PLH-PEG可以有效地抑制H22荷瘤小鼠的肿瘤生长。我们所设计的pH控制的智能开关系统有望为癌症治疗提供有价值的策略。(C)2017 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
A novel and intelligent pH-controlled system having an "on-off" switch based on poly(t-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.Statement of SignificanceA novel pH-controlled intelligent and reversible "on-off" switch system based on poly(-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. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.