Tailoring Macromolecular Expression at Polymersome Surfaces
Tailoring Macromolecular Expression at Polymersome Surfaces
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DOI：
10.1002/adfm.200900201
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发表时间：
2009-09-23
影响因子：
19
通讯作者：
Ryan, Anthony J.
中科院分区：
文献类型：
--
作者：
Blanazs, Adam;Massignani, Marzia;Ryan, Anthony J.
采用原子转移自由基聚合法合成了一系列两亲性ABC三嵌段共聚物，其中A和C嵌段为亲水性嵌段，B嵌段为pH敏感性嵌段，在酸性溶液中可由亲水性转变为疏水性嵌段。小心地向酸性溶液中的分子溶解的共聚物中添加碱容易诱导此类三嵌段共聚物在中性pH附近自组装以形成pH敏感性聚合物囊泡（也称为聚合物囊泡）。囊泡）具有不对称的膜。通过“A”和“C”嵌段的相对体积分数的系统变化，可以选择在聚合物囊泡的内部或外部冠处表达的聚合物链的化学性质。用这些不对称聚合物囊泡处理原代人真皮成纤维细胞证明了这种空间分离的生物学后果，其中聚合物囊泡细胞毒性和内吞率都由聚合物囊泡表面化学性质决定。聚合物囊泡的pH敏感性质容易促进它们在内吞作用后的解离，这是由于相对低的内体pH，这导致包封的染料的快速释放。选择性结合的阴离子底物，如DNA内的阳离子聚合物囊泡体积，加上一个生物相容性的外部，导致潜在的基因传递应用这些pH敏感的不对称纳米载体。
A series of amphiphilic ABC triblock copolymers are synthesized by atom transfer radical polymerization, wherein the 'A' and 'C' blocks are hydrophilic and the pH-sensitive 'B' block can be switched from hydrophilic in acidic solution to hydrophobic at pH 7. Careful addition to base to the molecularly dissolved copolymer in acidic solution readily induces the self-assembly of such triblock copolymers at around neutral pH to form pH-sensitive polymersomes (a.k.a. vesicles) with asymmetric membranes. By systematic variation of the relative volume fractions of the 'A' and 'C' blocks, the chemical nature of the polymer chains expressed at the interior or exterior corona of the polymersomes can be selected. Treatment of primary human dermal fibroblast cells with these asymmetric polymersomes demonstrates the biological consequences of such spatial segregation, with both polymersome cytotoxicity and endocytosis rates being dictated by the nature of the polymersome surface chemistry. The pH-sensitive nature of the polymersomes readily facilitates their dissociation after endocytosis due to the relatively low endosomal pH, which results in the rapid release of an encapsulated dye. Selective binding of anionic substrates such as DNA within the inner cationic polymersome volume, coupled with a biocompatible exterior, leads to potential gene delivery applications for these pH-sensitive asymmetric nanovectors.