In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents.
In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents.
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DOI：
10.1016/j.ab.2011.09.024
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发表时间：
2012-02-15
影响因子：
2.9
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Chen B;Shah SS;Shin Y;Lei C;Liu J
我们报道在不同的生理条件下，生物分子药物可以储存在纳米孔载体中，然后在需要急性反应时立即释放，生物分子药物分子也可以在很长时间内逐渐从纳米孔载体中释放出来，以实现完全恢复。有机磷酸失水解酶(OPAA)由于主要的静电相互作用被自发地包裹在官能化介孔二氧化硅(FMS)中。OPAA-FMS复合材料在pH 9.0、NaHCO3-Na2CO3缓冲体系中呈突释，在pH 7.4的模拟体液中呈缓释。OPAA与NH2-FMS的结合可以减少OPAA分子在水环境中的色氨酸暴露。FMS中结合的OPAA的活性低于酶包埋前溶液中的游离OPAA。但释放的酶仍具有天然的构象结构和与酶包埋前相同的高酶活性。在兔血清中的体外实验结果表明，OPAA-FMS和释放的OPAA都可以作为对抗有机磷神经毒剂的药物措施。
We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterwards can be instantly released when needed for acute responses, and the biomolecular drug molecules can also be gradually released from the nanoporous support over a long time for a complete recovery. Organophosphorus acid anhydrolase (OPAA) was spontaneously and largely entrapped in functionalized mesoporous silica (FMS) due to the dominant electrostatic interaction. The OPAA-FMS composite exhibited a burst release in pH 9.0, NaHCO3-Na2CO3 buffer system and a gradual release in pH 7.4, simulated body fluid. The binding of OPAA to NH2-FMS can result in less Trp exposure of OPAA molecules to aqueous environment. The bound OPAA in FMS displayed lower activity than the free OPAA in solution prior to the enzyme entrapment. However, the released enzyme still displayed the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. The in vitro results in the rabbit serum demonstrate that both OPAA-FMS and the released OPAA may be used as the medical measures against the organophosphorus nerve agents.
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DOI：
10.1016/j.bbrc.2009.10.112
发表时间：
2009-12-25
影响因子：
3.1
作者：
Chen, Baowei;Lei, Chenghong;Shin, Yongsoon;Liu, Jun
通讯作者：
Liu, Jun
影响因子：
5.8
作者：
ELLMAN, GL;COURTNEY, KD;FEATHERSTONE, RM
通讯作者：
FEATHERSTONE, RM
影响因子：
3.8
作者：
Petrikovics, I;Cheng, TC;Way, JL
通讯作者：
Way, JL
影响因子：
2.9
作者：
Vyas, Nand K.;Nickitenko, Alexei;Quiocho, Florante A.
通讯作者：
Quiocho, Florante A.
影响因子：
56.9
作者：
Feng, X;Fryxell, GE;Kemner, KM
通讯作者：
Kemner, KM