Stimulus-responsive controlled release system by covalent immobilization of an enzyme into mesoporous silica nanoparticles.
Stimulus-responsive controlled release system by covalent immobilization of an enzyme into mesoporous silica nanoparticles.
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DOI：
10.1021/bc200301a
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发表时间：
2012-04-18
影响因子：
4.7
通讯作者：
Griebenow, Kai
中科院分区：
文献类型：
--
作者：
Mendez, Jessica;Monteagudo, Alina;Griebenow, Kai
介孔二氧化硅纳米颗粒（MSN）已成为一类有吸引力的药物递送载体的治疗剂。在此，我们探索了共价固定蛋白质到MSN，以产生一个刺激响应控制释放系统。首先，使用（巯丙基）-三甲氧基硅烷（MPTMS）用硫醇基团官能化MSN。通过X射线光电子能谱（XP）、傅里叶变换红外（FTIR）光谱和动态光散射来验证官能化。以1：1的低比例将模型酶碳酸酐酶（CA）与磺基琥珀酰亚胺基6-[3 '（2-吡啶基二硫代）-丙酰胺基]己酸酯（Sulfo-LC-SPDP）偶联以防止酶失活，随后通过硫醇-二硫键交换共价固定到MSN中。该酶可在代表细胞内氧化还原条件的10 mM谷胱甘肽存在下从MSN中释放，而在代表1 μM谷胱甘肽的细胞外氧化还原条件下仍与MSN结合。释放的酶的活性>80%，表明该酶在固定和释放后仍然具有很大的功能和活性。将人宫颈癌（HeLa）细胞与各种浓度的MSN-CA生物缀合物一起孵育24小时，数据显示出良好的生物相容性。总之，我们证明了MSN作为蛋白质潜在药物递送系统的潜力。
Mesoporous silica nanoparticles (MSN) have emerged as an attractive class of drug delivery carriers for therapeutic agents. Herein, we explored the covalent immobilization of proteins into MSN to generate a stimulus-responsive controlled release system. First, MSN were functionalized with thiol groups using (mercaptopropyl)-trimethoxysilane (MPTMS). Functionalization was verified by X-ray photoelectron spectroscopy (XP), Fourier-transform infrared (FTIR) spectroscopy, and dynamic light scattering. The model enzyme carbonic anhydrase (CA) was coupled to sulfosuccinimidyl 6-[3'(2-pyridyldithio)-propionamido]hexanoate (Sulfo-LC-SPDP) at a low ratio of 1:1 to prevent enzyme inactivation and subsequently covalently immobilized into MSN via thiol-disulfide interchange. The enzyme could be released from MSN with 10 mM glutathione which represents intra-cellular redox conditions while it remained bound to the MSN at extra-cellular redox conditions represented by 1 μM glutathione. The activity of the released enzyme was >80% demonstrating that the enzyme was still largely functional and active after immobilization and release. Human cervical cancer (HeLa) cells were incubated with the MSN-CA bioconjugates at various concentrations for 24 h and the data show good biocompatibility. In summary, we demonstrate the potential of MSN as potential drug delivery systems for proteins.
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影响因子：
16.2
作者：
CORY, AH;OWEN, TC;CORY, JG
通讯作者：
CORY, JG
影响因子：
8.6
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DOI：
10.1107/s0907444904003166
发表时间：
2004-04-01
影响因子：
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作者：
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通讯作者：
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影响因子：
15
作者：
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通讯作者：
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