Charge-reversal plug gate nanovalves on peptide-functionalized mesoporous silica nanoparticles for targeted drug delivery.
Charge-reversal plug gate nanovalves on peptide-functionalized mesoporous silica nanoparticles for targeted drug delivery.
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DOI：
10.1039/c3tb20792g
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发表时间：
2013-10
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通讯作者：
G. Luo;Weihai Chen;Yun Liu;Jing Zhang;Si-Xue Cheng;R. Zhuo;Xianzheng Zhang
中科院分区：
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作者：
G. Luo;Weihai Chen;Yun Liu;Jing Zhang;Si-Xue Cheng;R. Zhuo;Xianzheng Zhang
为了开发用于生物医学应用的介孔二氧化硅纳米颗粒（MSN）上的智能纳米阀，设计了一种新型的具有插栅纳米阀（PGN）的肽官能化MSN，用于在癌细胞中靶向释放药物。MSN的外壳通过点击化学用K8肽（八赖氨酸序列）官能化，然后通过α，β-不饱和键与柠康酸酐反应以制备带负电荷的MSN-K8（Cit）。随后，通过静电相互作用将含有两个用于靶向的Arg-Gly-Asp（RGD）序列的阳离子K8（RGD）2肽引入到MSN-K8（Cit）的带负电荷的表面以形成PGN。发现，在pH 5.0（模拟内/溶酶体环境）下，由于酸不稳定酰胺在酸性条件下的水解，MSN-K8（Cit）的表面电荷可以从-41 mV转换为+19 mV，这意味着随后的静电排斥诱导纳米阀的打开和抗癌药物DOX的释放。根据药物释放研究，79%的DOX在pH 5.0下在48小时内释放，而在pH 6.5和7.4下释放少得多的DOX。体外细胞实验证实，该药物缓释系统对αvβ3阳性的U87 MG癌细胞具有增强的细胞结合和细胞抑制作用。
To develop a smart nanovalve on mesoporous silica nanoparticles (MSNs) for biomedical applications, a new type of peptide-functionalized MSN with a plug-gate nanovalve (PGN) was designed for targeted drug release in cancer cells. The outer shell of MSN was functionalized with K8 peptide (octa-lysine sequence) by click chemistry, followed by reacting with citraconic anhydride viaα,β-unsaturated bond to prepare negatively charged MSN-K8(Cit). Subsequently, a cationic K8(RGD)2 peptide containing two Arg-Gly-Asp (RGD) sequences for targeting was introduced via electrostatic interaction to the negatively charged surface of MSN-K8(Cit) to form PGN. It was found that, at pH 5.0 (simulating the endo/lysosomal environment), the surface charge of MSN-K8(Cit) could convert from -41 mV to +19 mV due to the hydrolysis of the acid-labile amides in the acidic condition, implying the subsequent electrostatic repulsion to induce opening of the nanovalves and release of anticancer drug, DOX. According to the drug release studies, 79% of DOX was released within 48 h at pH 5.0, while much less DOX was released at pH 6.5 and 7.4. Furthermore, in vitro cellular experiments confirmed that the drug delivery system had enhanced cellular association and cell inhibition effect on αvβ3-positive U87 MG cancerous cells.