Axthelm Fabian, Casse Olivier, Koppenol Willem H, Nauser Thomas, Meier Wolfgang, Palivan Cornelia G
Department of Chemistry, University of Basel, Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
J Phys Chem B. 2008 Jul 17;112(28):8211-7. doi: 10.1021/jp803032w. Epub 2008 Jun 21.
We designed and tested an antioxidant nanoreactor based on encapsulation of Cu,Zn superoxide dismutase in amphiphilic copolymer nanovesicles, the membranes of which are oxygen permeable. The nanovesicles, made of poly(2-methyloxazoline)-poly(dimethylsiloxane)-poly(2-methyloxazoline), successfully encapsulated the protein during their self-assembling process, as proved by confocal laser-scanning microscopy and fluorescence-correlation spectroscopy. Electron paramagnetic resonance spectroscopy and circular dichroism analyses showed that no structural changes appeared in the protein molecules once inside the inner space of the nanovesicles. The function of this antioxidant nanoreactor was tested by pulse radiolysis, which demonstrated that superoxide dismutase remains active inside the nanovesicles and detoxifies the superoxide radical in situ. The membrane of our triblock copolymer nanovesicles plays a double role, both to shield the sensitive protein and to selectively let superoxide and dioxygen penetrate to its inner space. This simple and robust hybrid system provides a selective shielding of sensitive enzymes from proteolytic attack and therefore a new direction for developing drug delivery applications.
我们设计并测试了一种抗氧化纳米反应器，它基于将铜锌超氧化物歧化酶封装在两亲性共聚物纳米囊泡中，该纳米囊泡的膜具有透氧性。由聚（2-甲基恶唑啉）-聚（二甲基硅氧烷）-聚（2-甲基恶唑啉）制成的纳米囊泡在其自组装过程中成功封装了蛋白质，共聚焦激光扫描显微镜和荧光相关光谱证实了这一点。电子顺磁共振光谱和圆二色性分析表明，蛋白质分子一旦进入纳米囊泡内部空间，其结构不会发生变化。通过脉冲辐解测试了这种抗氧化纳米反应器的功能，结果表明超氧化物歧化酶在纳米囊泡内部仍保持活性，并能原位清除超氧自由基。我们的三嵌段共聚物纳米囊泡的膜起到双重作用，既能保护敏感蛋白质，又能选择性地让超氧和氧气渗透到其内部空间。这种简单而强大的混合系统为敏感酶提供了免受蛋白水解攻击的选择性保护，因此为开发药物递送应用提供了一个新方向。
