Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056 Basel, Switzerland.
Macromol Biosci. 2010 May 14;10(5):531-8. doi: 10.1002/mabi.200900379.
The bioavailability limitations of proteins make them difficult to be directly delivered, particularly in diseases caused by insufficient amounts or inactive variants of those proteins. Nanoreactors represent a new promising approach to overcome these limitations because they serve both to protect the protein in their aqueous interior, and simultaneously to allow the protein to act in situ. Here we examine an antioxidant nanoreactor based on SOD encapsulated in amphiphilic block copolymer nanovesicles, and analyze its behavior as a function of the copolymer composition. The membrane of the triblock copolymer nanovesicles plays a double role, both to shield the sensitive protein and selectively to let superoxide and dioxygen penetrate to its inner space. The encapsulation efficiency for different triblock copolymer vesicles was quantified by fluorescence correlation spectroscopy using a fluorescently labeled SOD. Pulse radiolysis experiments and an enzymatic assay were used to compare the permeability of the wall-forming membranes towards superoxide anions. While the encapsulation efficiency mainly depends on the vesicle dimensions, the membrane permeability is mainly affected by the length of the hydrophobic PDMS middle blocks of our polymers. For polymers with very long PDMS chains superoxide anion transport across the membranes was too slow to be detected by our experiments.
蛋白质的生物利用度限制使得它们难以直接递送，特别是在那些蛋白质的数量不足或活性变体引起的疾病中。纳米反应器是克服这些限制的一种很有前途的新方法，因为它们既可以保护蛋白质在其水相内部，又可以允许蛋白质在原位发挥作用。在这里，我们研究了一种基于 SOD 包封在两亲嵌段共聚物纳米囊泡中的抗氧化纳米反应器，并分析了其作为共聚物组成函数的行为。三嵌段共聚物纳米囊泡的膜具有双重作用，既能屏蔽敏感的蛋白质，又能选择性地让超氧化物和氧气渗透到其内部空间。用荧光标记的 SOD 通过荧光相关光谱法定量测定了不同嵌段共聚物囊泡的包封效率。脉冲辐射分解实验和酶分析实验用于比较形成囊泡的膜对超氧阴离子的渗透性。虽然包封效率主要取决于囊泡的尺寸，但膜的渗透性主要受我们聚合物中疏水 PDMS 中间块的长度影响。对于 PDMS 链非常长的聚合物，超氧阴离子通过膜的传输速度太慢，我们的实验无法检测到。
